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Conserved domains on  [gi|1039745905|ref|XP_017171440|]
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PX domain-containing protein kinase-like protein isoform X6 [Mus musculus]

Protein Classification

PX domain-containing protein kinase-like protein( domain architecture ID 10160724)

PX domain-containing protein kinase-like protein, also called MONaKA (Modulator of Na,K-ATPase), binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PX_MONaKA cd06871
The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain ...
13-132 1.68e-80

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


:

Pssm-ID: 132781  Cd Length: 120  Bit Score: 246.50  E-value: 1.68e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  13 LLDDTVPLTAAVEASQSLQSHTEYIIRVQRGISAENSWQIVRRYSDFDLLNNSLQITGLSLPLPPKKLIGNMDREFIAER 92
Cdd:cd06871     1 LLDDTVPLTCVIEASQNIQSHTEYIIRVQRGPSPENSWQVIRRYNDFDLLNASLQISGISLPLPPKKLIGNMDREFIAER 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039745905  93 QRGLQNYLNVIMANHVLSNCELLKKFLDPNNYSANYTEIA 132
Cdd:cd06871    81 QQGLQNYLNVILMNPILASCLPVKKFLDPNNYSANFTEIA 120
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
198-345 2.84e-10

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd00180:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 215  Bit Score: 59.98  E-value: 2.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIYKakpkdpflkkycnpkKTQGLELQQIKTYGRQILEALK 277
Cdd:cd00180    42 IEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE---------------NKGPLSEEEALSILRQLLSALE 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 278 FLHDKGFPYGHLHAANVMLD----------GNTCRLLDLENSLLGLPSFYRSYFT---QFRKINTLESVDVHCFGHLLYE 344
Cdd:cd00180   107 YLHSNGIIHRDLKPENILLDsdgtvkladfGLAKDLDSDDSLLKTTGGTTPPYYAppeLLGGRYYGPKVDIWSLGVILYE 186

                  .
gi 1039745905 345 M 345
Cdd:cd00180   187 L 187
 
Name Accession Description Interval E-value
PX_MONaKA cd06871
The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain ...
13-132 1.68e-80

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


Pssm-ID: 132781  Cd Length: 120  Bit Score: 246.50  E-value: 1.68e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  13 LLDDTVPLTAAVEASQSLQSHTEYIIRVQRGISAENSWQIVRRYSDFDLLNNSLQITGLSLPLPPKKLIGNMDREFIAER 92
Cdd:cd06871     1 LLDDTVPLTCVIEASQNIQSHTEYIIRVQRGPSPENSWQVIRRYNDFDLLNASLQISGISLPLPPKKLIGNMDREFIAER 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039745905  93 QRGLQNYLNVIMANHVLSNCELLKKFLDPNNYSANYTEIA 132
Cdd:cd06871    81 QQGLQNYLNVILMNPILASCLPVKKFLDPNNYSANFTEIA 120
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
44-122 1.73e-16

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 74.20  E-value: 1.73e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  44 ISAENSWQIVRRYSDFDLLNNSLQIT--GLSLP-LPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFLD 120
Cdd:pfam00787   3 TFSLEEWSVRRRYSDFVELHKKLLRKfpSVIIPpLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLE 82

                  ..
gi 1039745905 121 PN 122
Cdd:pfam00787  83 SD 84
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
32-120 3.04e-15

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 71.61  E-value: 3.04e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905   32 SHTEYIIRVQRGISAEnSWQIVRRYSDFDLLNNSLQIT--GLSLP-LPPKKLIG---NMDREFIAERQRGLQNYLNVIMA 105
Cdd:smart00312  11 KHYYYVIEIETKTGLE-EWTVSRRYSDFLELHSKLKKHfpRSILPpLPGKKLFGrlnNFSEEFIEKRRRGLEKYLQSLLN 89
                           90
                   ....*....|....*.
gi 1039745905  106 NHVLSN-CELLKKFLD 120
Cdd:smart00312  90 HPELINhSEVVLEFLE 105
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
198-345 2.84e-10

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 59.98  E-value: 2.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIYKakpkdpflkkycnpkKTQGLELQQIKTYGRQILEALK 277
Cdd:cd00180    42 IEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE---------------NKGPLSEEEALSILRQLLSALE 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 278 FLHDKGFPYGHLHAANVMLD----------GNTCRLLDLENSLLGLPSFYRSYFT---QFRKINTLESVDVHCFGHLLYE 344
Cdd:cd00180   107 YLHSNGIIHRDLKPENILLDsdgtvkladfGLAKDLDSDDSLLKTTGGTTPPYYAppeLLGGRYYGPKVDIWSLGVILYE 186

                  .
gi 1039745905 345 M 345
Cdd:cd00180   187 L 187
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
198-351 5.35e-08

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 54.07  E-value: 5.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  198 IKLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIykakpkdpflkkycnpKKTQGLELQQIKTYGRQILEALK 277
Cdd:smart00220  48 IKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLL----------------KKRGRLSEDEARFYLRQILSALE 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  278 FLHDKGFPYGHLHAANVMLDGNT---------CRLLDLE---NSLLGLPsFYRS-------YFTqfrkintlESVDVHCF 338
Cdd:smart00220 112 YLHSKGIVHRDLKPENILLDEDGhvkladfglARQLDPGeklTTFVGTP-EYMApevllgkGYG--------KAVDIWSL 182
                          170
                   ....*....|...
gi 1039745905  339 GHLLYEMTYGRPP 351
Cdd:smart00220 183 GVILYELLTGKPP 195
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
260-369 8.15e-07

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 51.55  E-value: 8.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 260 LELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGN-TCRLLDL-------------ENSLLGLPSfYRSYfTQFR 325
Cdd:COG0515   104 LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDgRVKLIDFgiaralggatltqTGTVVGTPG-YMAP-EQAR 181
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1039745905 326 KINTLESVDVHCFGHLLYEMTYGRPPdsvpvdsFPPASSLAVVA 369
Cdd:COG0515   182 GEPVDPRSDVYSLGVTLYELLTGRPP-------FDGDSPAELLR 218
COG5391 COG5391
Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function ...
33-111 8.82e-07

Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function prediction only];


Pssm-ID: 227680 [Multi-domain]  Cd Length: 524  Bit Score: 51.34  E-value: 8.82e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  33 HTEY-IIRVQRGISAENS----WQIVRRYSDFDLLNNSLQ---ITGLSLPLPPKKLI-----GNMDREFIAERQRGLQNY 99
Cdd:COG5391   151 HTSYeIITVTNLPSFQLResrpLVVRRRYSDFESLHSILIkllPLCAIPPLPSKKSNseyygDRFSDEFIEERRQSLQNF 230
                          90
                  ....*....|..
gi 1039745905 100 LNVIMANHVLSN 111
Cdd:COG5391   231 LRRVSTHPLLSN 242
PTZ00036 PTZ00036
glycogen synthase kinase; Provisional
229-399 7.41e-05

glycogen synthase kinase; Provisional


Pssm-ID: 173333 [Multi-domain]  Cd Length: 440  Bit Score: 45.03  E-value: 7.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 229 NEKGTLKDLIYKAKPKD--PFLKKYCnpKKTQGLELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGNT-----C 301
Cdd:PTZ00036  136 NEKNIFLNVVMEFIPQTvhKYMKHYA--RNNHALPLFLVKLYSYQLCRALAYIHSKFICHRDLKPQNLLIDPNThtlklC 213
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 302 RLLDLENSLLGLPS-------FYRSYFTQFRKINTLESVDVHCFGHLLYEMTYGRPpdsvpvdSFPPASSLAVVAVLEST 374
Cdd:PTZ00036  214 DFGSAKNLLAGQRSvsyicsrFYRAPELMLGATNYTTHIDLWSLGCIIAEMILGYP-------IFSGQSSVDQLVRIIQV 286
                         170       180
                  ....*....|....*....|....*.
gi 1039745905 375 LsceacknGMPTVSRLLQM-PLFSDV 399
Cdd:PTZ00036  287 L-------GTPTEDQLKEMnPNYADI 305
 
Name Accession Description Interval E-value
PX_MONaKA cd06871
The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain ...
13-132 1.68e-80

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


Pssm-ID: 132781  Cd Length: 120  Bit Score: 246.50  E-value: 1.68e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  13 LLDDTVPLTAAVEASQSLQSHTEYIIRVQRGISAENSWQIVRRYSDFDLLNNSLQITGLSLPLPPKKLIGNMDREFIAER 92
Cdd:cd06871     1 LLDDTVPLTCVIEASQNIQSHTEYIIRVQRGPSPENSWQVIRRYNDFDLLNASLQISGISLPLPPKKLIGNMDREFIAER 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039745905  93 QRGLQNYLNVIMANHVLSNCELLKKFLDPNNYSANYTEIA 132
Cdd:cd06871    81 QQGLQNYLNVILMNPILASCLPVKKFLDPNNYSANFTEIA 120
PX_domain cd06093
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
31-120 3.90e-22

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.


Pssm-ID: 132768 [Multi-domain]  Cd Length: 106  Bit Score: 91.27  E-value: 3.90e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  31 QSHTEYIIRVQRGIsaENSWQIVRRYSDFDLLNNSLQIT--GLSLP-LPPKKLIGNMDREFIAERQRGLQNYLNVIMANH 107
Cdd:cd06093    15 KKYVVYIIEVTTQG--GEEWTVYRRYSDFEELHEKLKKKfpGVILPpLPPKKLFGNLDPEFIEERRKQLEQYLQSLLNHP 92
                          90
                  ....*....|...
gi 1039745905 108 VLSNCELLKKFLD 120
Cdd:cd06093    93 ELRNSEELKEFLE 105
PX_SNX16 cd07276
The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a ...
34-119 1.09e-18

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.


Pssm-ID: 132809  Cd Length: 110  Bit Score: 81.69  E-value: 1.09e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  34 TEYIIRVQRgiSAENSWQIVRRYSDFDLLNNSL--QITGLSLPLPPKKLIG-NMDREFIAERQRGLQNYLNVIMANHVLS 110
Cdd:cd07276    21 TVYKIRVEN--KVGDSWFVFRRYTDFVRLNDKLkqMFPGFRLSLPPKRWFKdNFDPDFLEERQLGLQAFVNNIMAHKDIA 98

                  ....*....
gi 1039745905 111 NCELLKKFL 119
Cdd:cd07276    99 KCKLVREFF 107
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
44-122 1.73e-16

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 74.20  E-value: 1.73e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  44 ISAENSWQIVRRYSDFDLLNNSLQIT--GLSLP-LPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFLD 120
Cdd:pfam00787   3 TFSLEEWSVRRRYSDFVELHKKLLRKfpSVIIPpLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLE 82

                  ..
gi 1039745905 121 PN 122
Cdd:pfam00787  83 SD 84
PX_SNX8_Mvp1p_like cd06866
The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX ...
33-119 2.39e-15

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.


Pssm-ID: 132776  Cd Length: 105  Bit Score: 71.88  E-value: 2.39e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  33 HTEYIIRVQRGISaenswQIVRRYSDFDLLNNSLQ---ITGLSLPLPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVL 109
Cdd:cd06866    18 HVEYEVSSKRFKS-----TVYRRYSDFVWLHEYLLkryPYRMVPALPPKRIGGSADREFLEARRRGLSRFLNLVARHPVL 92
                          90
                  ....*....|
gi 1039745905 110 SNCELLKKFL 119
Cdd:cd06866    93 SEDELVRTFL 102
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
32-120 3.04e-15

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 71.61  E-value: 3.04e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905   32 SHTEYIIRVQRGISAEnSWQIVRRYSDFDLLNNSLQIT--GLSLP-LPPKKLIG---NMDREFIAERQRGLQNYLNVIMA 105
Cdd:smart00312  11 KHYYYVIEIETKTGLE-EWTVSRRYSDFLELHSKLKKHfpRSILPpLPGKKLFGrlnNFSEEFIEKRRRGLEKYLQSLLN 89
                           90
                   ....*....|....*.
gi 1039745905  106 NHVLSN-CELLKKFLD 120
Cdd:smart00312  90 HPELINhSEVVLEFLE 105
PX_RUN cd07277
The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX ...
48-142 1.83e-14

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.


Pssm-ID: 132810  Cd Length: 118  Bit Score: 69.68  E-value: 1.83e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  48 NSWQIVRRYSDFDLLNNSLQ-----ITglSLPLPPKKLIGNMDREFIAERQRGLQNYLNVIMaNHVLSNCELLkkfldpn 122
Cdd:cd07277    30 DEWNVYRRYSEFYELHKKLKkkfpvVR--SFDFPPKKAIGNKDAKFVEERRKRLQVYLRRVV-NTLIQTSPEL------- 99
                          90       100
                  ....*....|....*....|
gi 1039745905 123 nySANYTEIALQQVSMFFRS 142
Cdd:cd07277   100 --TACPSKETLIKLLPFFGD 117
PX_IRAS cd06875
The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor ...
19-124 9.15e-14

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132785  Cd Length: 116  Bit Score: 67.69  E-value: 9.15e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  19 PLTAAVEASQSLQSHTEYIIRVQRGisaENSWQIVRRYSDFDLLNNSL--QITGLSLPLPPKKLIGNMDREFIAERQRGL 96
Cdd:cd06875     3 ETKIRIPSAETVEGYTVYIIEVKVG---SVEWTVKHRYSDFAELHDKLvaEHKVDKDLLPPKKLIGNKSPSFVEKRRKEL 79
                          90       100
                  ....*....|....*....|....*...
gi 1039745905  97 QNYLNVIMANHVLSNCELLKKFLDPNNY 124
Cdd:cd06875    80 EIYLQTLLSFFQKTMPRELAHFLDFHKY 107
PX_SNX13 cd06873
The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a ...
36-121 1.12e-12

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.


Pssm-ID: 132783  Cd Length: 120  Bit Score: 64.60  E-value: 1.12e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  36 YIIRVQR--GISAENSWQIVRRYSDFDLLNNSL--QITGLS-LPLPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLS 110
Cdd:cd06873    25 YAISVTRiyPNGQEESWHVYRRYSDFHDLHMRLkeKFPNLSkLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLD 104
                          90
                  ....*....|....*
gi 1039745905 111 NC----ELLKKFLDP 121
Cdd:cd06873   105 ANpglqEIVLDFLEP 119
PX_SNX41_42 cd06867
The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX ...
31-122 2.38e-12

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.


Pssm-ID: 132777  Cd Length: 112  Bit Score: 63.42  E-value: 2.38e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  31 QSHTEYIIRVQrgisaenSWQIVRRYSDFDLLNNSLQI---TGLSLPLPPKKLIGNM---------DREFIAERQRGLQN 98
Cdd:cd06867    16 GSYIVYVIRLG-------GSEVKRRYSEFESLRKNLTRlypTLIIPPIPEKHSLKDYakkpskaknDAKIIERRKRMLQR 88
                          90       100
                  ....*....|....*....|....
gi 1039745905  99 YLNVIMANHVLSNCELLKKFLDPN 122
Cdd:cd06867    89 FLNRCLQHPILRNDIVFQKFLDPN 112
PX_YPT35 cd07280
The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain ...
37-121 3.26e-12

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.


Pssm-ID: 132813  Cd Length: 120  Bit Score: 63.50  E-value: 3.26e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  37 IIRVQRGISAENSWQIV--------------RRYSDFDLLNNSLQIT-----GLSLP-LPPKKLI----GNMDREFIAER 92
Cdd:cd07280    12 IVGGDTGGGAYVVWKITietkdligssivayKRYSEFVQLREALLDEfprhkRNEIPqLPPKVPWydsrVNLNKAWLEKR 91
                          90       100
                  ....*....|....*....|....*....
gi 1039745905  93 QRGLQNYLNVIMANHVLSNCELLKKFLDP 121
Cdd:cd07280    92 RRGLQYFLNCVLLNPVFGGSPVVKEFLLP 120
PX_SNX14 cd06877
The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a ...
36-122 1.49e-11

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.


Pssm-ID: 132787  Cd Length: 119  Bit Score: 61.62  E-value: 1.49e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  36 YIIRVQR-----GISAENSWQIVRRYSDFDLLNNSL-QITGLS--LPLPPKKLIGNMDREFIAERQRGLQNYLNVIMANH 107
Cdd:cd06877    25 FCIEVERndrraKGHEPQHWSVLRRYNEFYVLESKLtEFHGEFpdAPLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKP 104
                          90
                  ....*....|....*
gi 1039745905 108 VLSNCELLKKFLDPN 122
Cdd:cd06877   105 ELRGSELLYDFLSPN 119
PX_CISK cd06870
The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The ...
49-119 1.53e-11

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.


Pssm-ID: 132780  Cd Length: 109  Bit Score: 61.27  E-value: 1.53e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039745905  49 SWQIVRRYSDFDLLNNSL--QITGLSLPLPPKKLIG-NMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd06870    33 SWFVFRRYAEFDKLYESLkkQFPASNLKIPGKRLFGnNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106
PX_KIF16B_SNX23 cd06874
The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The ...
28-141 1.66e-10

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132784  Cd Length: 127  Bit Score: 58.55  E-value: 1.66e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  28 QSLQSHTEYIIRVQrgiSAENSWQIVRRYSDFDLLNNSLQ---ITGLSLPLPPKKLIGNMDREFIAERQRGLQNYLN--- 101
Cdd:cd06874    13 QGKDEHFEFEVKIT---VLDETWTVFRRYSRFRELHKTMKlkyPEVAALEFPPKKLFGNKSERVAKERRRQLETYLRnff 89
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039745905 102 VIMANhvLSNCELLKKfldpnnYSANYTEIALQQVSMFFR 141
Cdd:cd06874    90 SVCLK--LPACPLYPK------VGRTLSKATLCDFSPFFR 121
PX_SNX10 cd06898
The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; The PX domain is a ...
54-109 2.10e-10

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.


Pssm-ID: 132808  Cd Length: 113  Bit Score: 58.11  E-value: 2.10e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  54 RRYSDFDLLNNSLQITGLSL---PLPPKKLIGNM-DREFIAERQRGLQNYLNVIMANHVL 109
Cdd:cd06898    41 RRYSEFVWLRNRLQKNALLIqlpSLPPKNLFGRFnNEGFIEERQQGLQDFLEKVLQTPLL 100
PX_SNX1_2_like cd06859
The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is ...
30-119 2.19e-10

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.


Pssm-ID: 132769 [Multi-domain]  Cd Length: 114  Bit Score: 57.97  E-value: 2.19e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  30 LQSHTEYIIRVQRGIS--AENSWQIVRRYSDFDLLNNSLQITGLSL---PLPPKKLIG--NMDREFIAERQRGLQNYLNV 102
Cdd:cd06859    15 MSAYVVYRVTTKTNLPdfKKSEFSVLRRYSDFLWLYERLVEKYPGRivpPPPEKQAVGrfKVKFEFIEKRRAALERFLRR 94
                          90
                  ....*....|....*..
gi 1039745905 103 IMANHVLSNCELLKKFL 119
Cdd:cd06859    95 IAAHPVLRKDPDFRLFL 111
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
198-345 2.84e-10

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 59.98  E-value: 2.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIYKakpkdpflkkycnpkKTQGLELQQIKTYGRQILEALK 277
Cdd:cd00180    42 IEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE---------------NKGPLSEEEALSILRQLLSALE 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 278 FLHDKGFPYGHLHAANVMLD----------GNTCRLLDLENSLLGLPSFYRSYFT---QFRKINTLESVDVHCFGHLLYE 344
Cdd:cd00180   107 YLHSNGIIHRDLKPENILLDsdgtvkladfGLAKDLDSDDSLLKTTGGTTPPYYAppeLLGGRYYGPKVDIWSLGVILYE 186

                  .
gi 1039745905 345 M 345
Cdd:cd00180   187 L 187
PX_SNX7_30_like cd06860
The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; The PX domain is ...
42-119 4.75e-10

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.


Pssm-ID: 132770  Cd Length: 116  Bit Score: 56.96  E-value: 4.75e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  42 RGISAENSWQIVRRYSDFDLLNNSLQI---TGLSLPLPPKK-LIGNMDR---EFIAERQRGLQNYLNVIMANHVLSNCEL 114
Cdd:cd06860    29 RSEFDSSEYSVRRRYQDFLWLRQKLEEshpTHIIPPLPEKHsVKGLLDRfspEFVATRMRALHKFLNRIVEHPVLSFNEH 108

                  ....*
gi 1039745905 115 LKKFL 119
Cdd:cd06860   109 LKVFL 113
PX_SNX20_21_like cd07279
The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain ...
37-119 5.75e-10

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.


Pssm-ID: 132812  Cd Length: 112  Bit Score: 56.57  E-value: 5.75e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  37 IIRVQRGISAENSWQIVRRYSDFDLLNNSLQ------ITGLSLPlpPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLS 110
Cdd:cd07279    23 LAVVQTGDPDTQPAFIERRYSDFLKLYKALRkqhpqlMAKVSFP--RKVLMGNFSSELIAERSRAFEQFLGHILSIPNLR 100

                  ....*....
gi 1039745905 111 NCELLKKFL 119
Cdd:cd07279   101 DSKAFLDFL 109
PX_Vps5p cd06861
The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain ...
32-119 1.96e-09

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.


Pssm-ID: 132771  Cd Length: 112  Bit Score: 55.05  E-value: 1.96e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  32 SHTEYIIRVQRGISAE--NSWQIVRRYSDFDLLNNSLQIT--GLSLPLPP-KKLIGNMDREFIAERQRGLQNYLNVIMAN 106
Cdd:cd06861    17 AHTVYTVRTRTTSPNFevSSFSVLRRYRDFRWLYRQLQNNhpGVIVPPPPeKQSVGRFDDNFVEQRRAALEKMLRKIANH 96
                          90
                  ....*....|...
gi 1039745905 107 HVLSNCELLKKFL 119
Cdd:cd06861    97 PVLQKDPDFRLFL 109
PX_SNARE cd06897
The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; The PX domain ...
25-120 4.64e-09

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132807  Cd Length: 108  Bit Score: 53.82  E-value: 4.64e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  25 EASQSLQSHTEYIIRVQrgiSAENSWQIVRRYSDFDLLNNSLQ-ITGLSLP--LPPKKLIGNM--DREFIAERQRGLQNY 99
Cdd:cd06897     7 TTSVSPKPYTVYNIQVR---LPLRSYTVSRRYSEFVALHKQLEsEVGIEPPypLPPKSWFLSTssNPKLVEERRVGLEAF 83
                          90       100
                  ....*....|....*....|...
gi 1039745905 100 LNVIM--ANHVLSNCELLKKFLD 120
Cdd:cd06897    84 LRALLndEDSRWRNSPAVKEFLN 106
PX_SNX4 cd06864
The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; The PX domain is a ...
54-119 1.74e-08

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.


Pssm-ID: 132774  Cd Length: 129  Bit Score: 53.14  E-value: 1.74e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039745905  54 RRYSDFDLLNNSLQITGLSL---PLPPKKL--------IGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd06864    50 RRYSEFELLRNYLVVTYPYVivpPLPEKRAmfmwqklsSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
198-351 5.35e-08

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 54.07  E-value: 5.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  198 IKLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIykakpkdpflkkycnpKKTQGLELQQIKTYGRQILEALK 277
Cdd:smart00220  48 IKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLL----------------KKRGRLSEDEARFYLRQILSALE 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  278 FLHDKGFPYGHLHAANVMLDGNT---------CRLLDLE---NSLLGLPsFYRS-------YFTqfrkintlESVDVHCF 338
Cdd:smart00220 112 YLHSKGIVHRDLKPENILLDEDGhvkladfglARQLDPGeklTTFVGTP-EYMApevllgkGYG--------KAVDIWSL 182
                          170
                   ....*....|...
gi 1039745905  339 GHLLYEMTYGRPP 351
Cdd:smart00220 183 GVILYELLTGKPP 195
PX_UP2_fungi cd06869
The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX ...
31-122 6.63e-08

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132779  Cd Length: 119  Bit Score: 51.13  E-value: 6.63e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  31 QSHTEYIIRVQRGISAENSWQIVRRYSDFDLLNNSL--QITGLSLPLPPKKLignmdrEFIAERQR-GLQNYLNVIMANH 107
Cdd:cd06869    31 KHHYEFIIRVRREGEEYRTIYVARRYSDFKKLHHDLkkEFPGKKLPKLPHKD------KLPREKLRlSLRQYLRSLLKDP 104
                          90
                  ....*....|....*
gi 1039745905 108 VLSNCELLKKFLDPN 122
Cdd:cd06869   105 EVAHSSILQEFLTSD 119
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
189-305 8.54e-08

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 53.52  E-value: 8.54e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 189 LSDKDFQCLIKLL-PSCVHPYIYRVTFATasESSALLIRAFNE---KGTLKDLIYKAKPkdpflkkycnpkktqgLELQQ 264
Cdd:cd14012    44 LLEKELESLKKLRhPNLVSYLAFSIERRG--RSDGWKVYLLTEyapGGSLSELLDSVGS----------------VPLDT 105
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1039745905 265 IKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGN----TCRLLD 305
Cdd:cd14012   106 ARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDagtgIVKLTD 150
PX_SNX15_like cd06881
The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; The PX ...
24-120 2.05e-07

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.


Pssm-ID: 132791  Cd Length: 117  Bit Score: 49.63  E-value: 2.05e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  24 VEASQSLQSHTEYII--RVQRGISAENSWQIV--RRYSDF-----DL--LNNSLQITGLSLPLPPKKLIGNMDREFIAER 92
Cdd:cd06881     8 TDTRRHKKGYTEYKItsKVFSRSVPEDVSEVVvwKRYSDFkklhrELsrLHKQLYLSGSFPPFPKGKYFGRFDAAVIEER 87
                          90       100
                  ....*....|....*....|....*...
gi 1039745905  93 QRGLQNYLNVIMANHVLSNCELLKKFLD 120
Cdd:cd06881    88 RQAILELLDFVGNHPALYQSSAFQQFFE 115
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
198-351 3.83e-07

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 51.43  E-value: 3.83e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIyrVTFATA--SESSALLIRAFNEKGTLKDLiykakpkdpfLKKYCNPkktqgLELQQIKTYGRQILEA 275
Cdd:cd05122    48 IAILKKCKHPNI--VKYYGSylKKDELWIVMEFCSGGSLKDL----------LKNTNKT-----LTEQQIAYVCKEVLKG 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 276 LKFLHDKGFPYGHLHAANVML---------D-GNTCRLLDL--ENSLLGLPsFYRSYfTQFRKINTLESVDVHCFGHLLY 343
Cdd:cd05122   111 LEYLHSHGIIHRDIKAANILLtsdgevkliDfGLSAQLSDGktRNTFVGTP-YWMAP-EVIQGKPYGFKADIWSLGITAI 188

                  ....*...
gi 1039745905 344 EMTYGRPP 351
Cdd:cd05122   189 EMAEGKPP 196
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
160-351 6.66e-07

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 51.23  E-value: 6.66e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 160 RKKYFLMKIknqpkerlvlswadLGPDKYLSDKDFQC-LIK---LLPSCVHPYIYRV--TFATasESSALLIRAFNEKGt 233
Cdd:cd05592    19 TNQYFAIKA--------------LKKDVVLEDDDVECtMIErrvLALASQHPFLTHLfcTFQT--ESHLFFVMEYLNGG- 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 234 lkDLIYKAKPKDPFlkkycnpkktqglELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGN---------TCRL- 303
Cdd:cd05592    82 --DLMFHIQQSGRF-------------DEDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLLDREghikiadfgMCKEn 146
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039745905 304 LDLEN---SLLGLPSFYRSYFTQFRKINtlESVDVHCFGHLLYEMTYGRPP 351
Cdd:cd05592   147 IYGENkasTFCGTPDYIAPEILKGQKYN--QSVDWWSFGVLLYEMLIGQSP 195
PX_SNX18 cd07286
The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a ...
51-119 7.95e-07

The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.


Pssm-ID: 132819  Cd Length: 127  Bit Score: 48.13  E-value: 7.95e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039745905  51 QIVRRYSDFDLLNNSL--QITGLSLP-LPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd07286    33 QVHRRYKHFDWLYARLaeKFPVISVPhIPEKQATGRFEEDFISKRRKGLIWWMDHMCSHPVLARCDAFQHFL 104
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
260-369 8.15e-07

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 51.55  E-value: 8.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 260 LELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGN-TCRLLDL-------------ENSLLGLPSfYRSYfTQFR 325
Cdd:COG0515   104 LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDgRVKLIDFgiaralggatltqTGTVVGTPG-YMAP-EQAR 181
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1039745905 326 KINTLESVDVHCFGHLLYEMTYGRPPdsvpvdsFPPASSLAVVA 369
Cdd:COG0515   182 GEPVDPRSDVYSLGVTLYELLTGRPP-------FDGDSPAELLR 218
COG5391 COG5391
Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function ...
33-111 8.82e-07

Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function prediction only];


Pssm-ID: 227680 [Multi-domain]  Cd Length: 524  Bit Score: 51.34  E-value: 8.82e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  33 HTEY-IIRVQRGISAENS----WQIVRRYSDFDLLNNSLQ---ITGLSLPLPPKKLI-----GNMDREFIAERQRGLQNY 99
Cdd:COG5391   151 HTSYeIITVTNLPSFQLResrpLVVRRRYSDFESLHSILIkllPLCAIPPLPSKKSNseyygDRFSDEFIEERRQSLQNF 230
                          90
                  ....*....|..
gi 1039745905 100 LNVIMANHVLSN 111
Cdd:COG5391   231 LRRVSTHPLLSN 242
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
146-407 9.12e-07

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 50.80  E-value: 9.12e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 146 WEVVEPLKDIGWRirKKYflmkiKNQPKERLVLSWADLGPDKYLSD-KDFQCLIKLLPSCVHPYIYRVTFATASESSALL 224
Cdd:cd06644    14 WEIIGELGDGAFG--KVY-----KAKNKETGALAAAKVIETKSEEElEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWI 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 225 IRAFNEKGTLKDLIYKAKpkdpflkkycnpkktQGLELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVML--DGN--- 299
Cdd:cd06644    87 MIEFCPGGAVDAIMLELD---------------RGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLtlDGDikl 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 300 --------TCRLLDLENSLLGLPSFYRSYFTQFRKINTLE---SVDVHCFGHLLYEMTYGRPP---------------DS 353
Cdd:cd06644   152 adfgvsakNVKTLQRRDSFIGTPYWMAPEVVMCETMKDTPydyKADIWSLGITLIEMAQIEPPhhelnpmrvllkiakSE 231
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039745905 354 VPVDSFPPASSLAVVAVLESTLscEACKNGMPTVSRLLQMPLFSDVlltTSEKP 407
Cdd:cd06644   232 PPTLSQPSKWSMEFRDFLKTAL--DKHPETRPSAAQLLEHPFVSSV---TSNRP 280
PX_SNX25 cd06878
The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; The PX domain is a ...
50-121 9.26e-07

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.


Pssm-ID: 132788  Cd Length: 127  Bit Score: 48.14  E-value: 9.26e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039745905  50 WQIVRRYSDFDLLNNSLQ-----ITGLSLPLPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFLDP 121
Cdd:cd06878    50 WVVTRKLSEFHDLHRKLKecsswLKKVELPSLSKKWFKSIDKKFLDKSKNQLQKYLQFILEDETLCQSEALYSFLSP 126
PX_MDM1p cd06876
The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a ...
24-119 1.56e-06

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132786  Cd Length: 133  Bit Score: 47.30  E-value: 1.56e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  24 VEASQSLQSHTEYIIRVQR--GISAENSWQIVRRYSDFDLLNNSLQITG---LSLPLPPKKLIG--NMDREFIAERQRGL 96
Cdd:cd06876    29 SDVEEEGKEFVVYLIEVQRlnNDDQSSGWVVARRYSEFLELHKYLKKRYpgvLKLDFPQKRKISlkYSKTLLVEERRKAL 108
                          90       100
                  ....*....|....*....|...
gi 1039745905  97 QNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd06876   109 EKYLQELLKIPEVCEDEEFRKFL 131
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
192-351 1.74e-06

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 49.53  E-value: 1.74e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 192 KDFQCLIKLLPSCVHPYIyrVTFATA----SESSALLIRAFNEKGTLKDliykakpkdpFLKKYCNPKktqgleLQQIKT 267
Cdd:cd13983    45 QRFKQEIEILKSLKHPNI--IKFYDSweskSKKEVIFITELMTSGTLKQ----------YLKRFKRLK------LKVIKS 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 268 YGRQILEALKFLHDKGFPYGH--LHAANVMLDGNT--CRLLDL----------ENSLLGLPSF-----YRSYFTqfrkin 328
Cdd:cd13983   107 WCRQILEGLNYLHTRDPPIIHrdLKCDNIFINGNTgeVKIGDLglatllrqsfAKSVIGTPEFmapemYEEHYD------ 180
                         170       180
                  ....*....|....*....|...
gi 1039745905 329 tlESVDVHCFGHLLYEMTYGRPP 351
Cdd:cd13983   181 --EKVDIYAFGMCLLEMATGEYP 201
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
198-394 2.12e-06

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 49.32  E-value: 2.12e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLiykakpkdpfLKKYcnpkktQGLELQQIKTYGRQILEALK 277
Cdd:cd06632    53 IALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGGSIHKL----------LQRY------GAFEEPVIRLYTRQILSGLA 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 278 FLHDKGFPYGHLHAANVMLDGN-TCRLLD------LENSLLGLpSFYRSYF-------TQFRKINTLEsVDVHCFGHLLY 343
Cdd:cd06632   117 YLHSRNTVHRDIKGANILVDTNgVVKLADfgmakhVEAFSFAK-SFKGSPYwmapeviMQKNSGYGLA-VDIWSLGCTVL 194
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039745905 344 EMTYGRPP--DSVPVDSFPPASSLAVVAVLESTLSCEA--------CKNG--MPTVSRLLQMP 394
Cdd:cd06632   195 EMATGKPPwsQYEGVAAIFKIGNSGELPPIPDHLSPDAkdfirlclQRDPedRPTASQLLEHP 257
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
143-314 2.16e-06

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 49.25  E-value: 2.16e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 143 EPKWEVVEPLKDigwrirkKYFLMKIKNQPKERLVLSWADLGPDKYLSD-KDFQCLIKLLPSCVHPYIYRVTFATASESS 221
Cdd:cd06643     4 EDFWEIVGELGD-------GAFGKVYKAQNKETGILAAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLDAFYYENN 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 222 ALLIRAFNEKGTLKDLIYKAKpkdpflkkycnpkktQGLELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVM--LDGN 299
Cdd:cd06643    77 LWILIEFCAGGAVDAVMLELE---------------RPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILftLDGD 141
                         170       180
                  ....*....|....*....|....*.
gi 1039745905 300 -----------TCRLLDLENSLLGLP 314
Cdd:cd06643   142 ikladfgvsakNTRTLQRRDSFIGTP 167
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
183-416 3.33e-06

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 49.17  E-value: 3.33e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 183 LGPDKYLSDKDFQCLIK----LLPSCVHPYIYRVTFATASESSALLIRAFNEKGtlkDLIYKAKPKDPFlkkycnpkktq 258
Cdd:cd05620    28 LKKDVVLIDDDVECTMVekrvLALAWENPFLTHLYCTFQTKEHLFFVMEFLNGG---DLMFHIQDKGRF----------- 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 259 glELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGN-TCRLLDL----EN--------SLLGLPSFYRSYFTQFR 325
Cdd:cd05620    94 --DLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDgHIKIADFgmckENvfgdnrasTFCGTPDYIAPEILQGL 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 326 KINTleSVDVHCFGHLLYEMTYGRPP----------DSVPVDS--FPPASSLAVVAVLESTLSCEACKNgMPTVSRLLQM 393
Cdd:cd05620   172 KYTF--SVDWWSFGVLLYEMLIGQSPfhgddedelfESIRVDTphYPRWITKESKDILEKLFERDPTRR-LGVVGNIRGH 248
                         250       260
                  ....*....|....*....|...
gi 1039745905 394 PLFSDVLLTTSEKPQFKIPTKLK 416
Cdd:cd05620   249 PFFKTINWTALEKRELDPPFKPK 271
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
198-305 4.06e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 48.29  E-value: 4.06e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIYRVtFATASESSALLIraFNE---KGTLKDLIykakpkdpflkkycnpKKTQGLELQQIKTYGRQILE 274
Cdd:cd06606    50 IRILSSLKHPNIVRY-LGTERTENTLNI--FLEyvpGGSLASLL----------------KKFGKLPEPVVRKYTRQILE 110
                          90       100       110
                  ....*....|....*....|....*....|..
gi 1039745905 275 ALKFLHDKGFPYGHLHAANVMLDGN-TCRLLD 305
Cdd:cd06606   111 GLEYLHSNGIVHRDIKGANILVDSDgVVKLAD 142
PX_SNX20 cd07300
The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; The PX domain is a ...
27-105 4.56e-06

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.


Pssm-ID: 132833  Cd Length: 114  Bit Score: 45.58  E-value: 4.56e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  27 SQSLQSHTEY-IIRVQRGISAENSWQIVRRYSDFDLLNNSLqITGLS-----LPLPPKKLIGNMDREFIAERQRGLQNYL 100
Cdd:cd07300    12 EQTISKHVVYqIIVIQTGSFDCNKVVIERRYSDFLKLHQEL-LSDFSeeledVVFPKKKLTGNFSEEIIAERRVALRDYL 90

                  ....*
gi 1039745905 101 NVIMA 105
Cdd:cd07300    91 TLLYS 95
PX_SNX_like cd06865
The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a ...
32-119 1.71e-05

The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.


Pssm-ID: 132775  Cd Length: 120  Bit Score: 44.33  E-value: 1.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  32 SHTEYIIRVQRGISAENS--WQIVRRYSDFDLLNNSLQIT--GLSLPLPPKKL----IGNMDREFIAERQRGLQNYLNVI 103
Cdd:cd06865    22 PYISYKVTTRTNIPSYTHgeFTVRRRFRDVVALADRLAEAyrGAFVPPRPDKSvvesQVMQSAEFIEQRRVALEKYLNRL 101
                          90
                  ....*....|....*.
gi 1039745905 104 MANHVLSNCELLKKFL 119
Cdd:cd06865   102 AAHPVIGLSDELRVFL 117
PX_SNX9 cd07285
The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; The PX domain is a ...
30-120 1.76e-05

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.


Pssm-ID: 132818  Cd Length: 126  Bit Score: 44.24  E-value: 1.76e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  30 LQSHTEYiirvqrGISAENSWQIV-RRYSDFDLLNNSLQIT-GLSLP---LPPKKLIGNMDREFIAERQRGLQNYLNVIM 104
Cdd:cd07285    17 LKSYIEY------QLTPTNTNRSVnHRYKHFDWLYERLLVKfGLAIPipsLPDKQVTGRFEEEFIKMRMERLQAWMTRMC 90
                          90
                  ....*....|....*.
gi 1039745905 105 ANHVLSNCELLKKFLD 120
Cdd:cd07285    91 RHPVISESEVFQQFLN 106
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
183-351 2.33e-05

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 46.44  E-value: 2.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 183 LGPDKYLSDKDFQCLIK----LLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIYKAKPKDPFLKKYcnpkktq 258
Cdd:cd05590    28 LKKDVILQDDDVECTMTekriLSLARNHPFLTQLYCCFQTPDRLFFVMEFVNGGDLMFHIQKSRRFDEARARF------- 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 259 glelqqiktYGRQILEALKFLHDKGFPYGHLHAANVMLDGNT-CRLLD------------LENSLLGLPSFYRSYFTQFR 325
Cdd:cd05590   101 ---------YAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGhCKLADfgmckegifngkTTSTFCGTPDYIAPEILQEM 171
                         170       180
                  ....*....|....*....|....*.
gi 1039745905 326 KINTleSVDVHCFGHLLYEMTYGRPP 351
Cdd:cd05590   172 LYGP--SVDWWAMGVLLYEMLCGHAP 195
PX_Atg24p cd06863
The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation ...
46-119 2.67e-05

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132773  Cd Length: 118  Bit Score: 43.43  E-value: 2.67e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  46 AENSWQIVRRYSDFDLLNNSLQ---ITGLSLPLPPKKLIGNM--DR---EFIAERQRGLQNYLNVIMANHVLSNCELLKK 117
Cdd:cd06863    34 SRKEFKVRRRYSDFVFLHECLSndfPACVVPPLPDKHRLEYItgDRfspEFITRRAQSLQRFLRRISLHPVLSQSKILHQ 113

                  ..
gi 1039745905 118 FL 119
Cdd:cd06863   114 FL 115
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
190-426 2.72e-05

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 45.73  E-value: 2.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 190 SDKDFQCLIKLLPSCVHPYIYRV-TFATASESSaLLIRAFNEKGTLKDLIYKAKPKDPflkkycnpkktqgLELQQIKTY 268
Cdd:cd14066    33 SKKEFLTELEMLGRLRHPNLVRLlGYCLESDEK-LLVYEYMPNGSLEDRLHCHKGSPP-------------LPWPQRLKI 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 269 GRQILEALKFLHDKGFP---YGHLHAANVMLDGNT---------CRLLDLENSLL------GLPSFYRSYFTQFRKINTl 330
Cdd:cd14066    99 AKGIARGLEYLHEECPPpiiHGDIKSSNILLDEDFepkltdfglARLIPPSESVSktsavkGTIGYLAPEYIRTGRVST- 177
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 331 eSVDVHCFGHLLYEMTYGRPpdsvPVDSFPPASSLavvavleSTLSCEACKNGMPTVSRLLQMPLFSDVLLTTSEkpqfk 410
Cdd:cd14066   178 -KSDVYSFGVVLLELLTGKP----AVDENRENASR-------KDLVEWVESKGKEELEDILDKRLVDDDGVEEEE----- 240
                         250
                  ....*....|....*.
gi 1039745905 411 iptkLKEALRIAKECI 426
Cdd:cd14066   241 ----VEALLRLALLCT 252
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
268-351 5.52e-05

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 45.28  E-value: 5.52e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 268 YGRQILEALKFLHDKGFPYGHLHAANVMLDGNT-CRLLD------------LENSLLGLPSF-------YRSY-Ftqfrk 326
Cdd:cd05570   101 YAAEICLALQFLHERGIIYRDLKLDNVLLDAEGhIKIADfgmckegiwggnTTSTFCGTPDYiapeilrEQDYgF----- 175
                          90       100
                  ....*....|....*....|....*
gi 1039745905 327 intleSVDVHCFGHLLYEMTYGRPP 351
Cdd:cd05570   176 -----SVDWWALGVLLYEMLAGQSP 195
PX_SNX3 cd07293
The phosphoinositide binding Phox Homology domain of Sorting Nexin 3; The PX domain is a ...
54-119 7.23e-05

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX3 associates with early endosomes through a PX domain-mediated interaction with phosphatidylinositol-3-phosphate (PI3P). It associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer. SNX3 is required for the formation of multivesicular bodies, which function as transport intermediates to late endosomes. It also promotes cell surface expression of the amiloride-sensitive epithelial Na+ channel (ENaC), which is critical in sodium homeostasis and maintenance of extracellular fluid volume.


Pssm-ID: 132826  Cd Length: 123  Bit Score: 42.29  E-value: 7.23e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039745905  54 RRYSDFDLLNNSLQITGLSL--PLPPKKLI---------GNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd07293    42 RRYSDFEWLRSELERESKVVvpPLPGKALFrqlpfrgddGIFDDSFIEERKQGLEQFLNKVAGHPLAQNERCLHMFL 118
PTZ00036 PTZ00036
glycogen synthase kinase; Provisional
229-399 7.41e-05

glycogen synthase kinase; Provisional


Pssm-ID: 173333 [Multi-domain]  Cd Length: 440  Bit Score: 45.03  E-value: 7.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 229 NEKGTLKDLIYKAKPKD--PFLKKYCnpKKTQGLELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGNT-----C 301
Cdd:PTZ00036  136 NEKNIFLNVVMEFIPQTvhKYMKHYA--RNNHALPLFLVKLYSYQLCRALAYIHSKFICHRDLKPQNLLIDPNThtlklC 213
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 302 RLLDLENSLLGLPS-------FYRSYFTQFRKINTLESVDVHCFGHLLYEMTYGRPpdsvpvdSFPPASSLAVVAVLEST 374
Cdd:PTZ00036  214 DFGSAKNLLAGQRSvsyicsrFYRAPELMLGATNYTTHIDLWSLGCIIAEMILGYP-------IFSGQSSVDQLVRIIQV 286
                         170       180
                  ....*....|....*....|....*.
gi 1039745905 375 LsceacknGMPTVSRLLQM-PLFSDV 399
Cdd:PTZ00036  287 L-------GTPTEDQLKEMnPNYADI 305
PX_SNX12 cd07294
The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; The PX domain is a ...
54-128 9.85e-05

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. The specific function of SNX12 has yet to be elucidated.


Pssm-ID: 132827  Cd Length: 132  Bit Score: 42.33  E-value: 9.85e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  54 RRYSDFDLLNNSLQITG--LSLPLPPKKLI---------GNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFLDPN 122
Cdd:cd07294    44 RRYSDFEWLKNELERDSkiVVPPLPGKALKrqlpfrgdeGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQDE 123

                  ....*.
gi 1039745905 123 NYSANY 128
Cdd:cd07294   124 TIDRNY 129
PX_SNX7 cd07284
The phosphoinositide binding Phox Homology domain of Sorting Nexin 7; The PX domain is a ...
37-119 9.92e-05

The phosphoinositide binding Phox Homology domain of Sorting Nexin 7; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX7 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, SNX30, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX7 has yet to be elucidated.


Pssm-ID: 132817  Cd Length: 116  Bit Score: 41.89  E-value: 9.92e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  37 IIRVQRGISAENSWQIVRRYSDFDLLNNSLQITGLSLPLPP-------KKLIGNMDREFIAERQRGLQNYLNVIMANHVL 109
Cdd:cd07284    24 MTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPlpekfvmKGMVERFNEDFIETRRKALHKFLNRIADHPTL 103
                          90
                  ....*....|
gi 1039745905 110 SNCELLKKFL 119
Cdd:cd07284   104 TFNEDFKIFL 113
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
199-351 1.25e-04

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 44.12  E-value: 1.25e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 199 KLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIYKAKpkdpflkkycnpkkTQGLELQQIKTYGRQILEALKF 278
Cdd:cd05607    54 EILEKVNSPFIVSLAYAFETKTHLCLVMSLMNGGDLKYHIYNVG--------------ERGIEMERVIFYSAQITCGILH 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 279 LHDKGFPYGHLHAANVMLDGN-TCRLLDLENSLL---GLPSFYRSYFTQFRKINTLE------SVDVHCFGHLLYEMTYG 348
Cdd:cd05607   120 LHSLKIVYRDMKPENVLLDDNgNCRLSDLGLAVEvkeGKPITQRAGTNGYMAPEILKeesysyPVDWFAMGCSIYEMVAG 199

                  ...
gi 1039745905 349 RPP 351
Cdd:cd05607   200 RTP 202
PX_SNX3_like cd06894
The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related proteins; The ...
54-119 1.34e-04

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.


Pssm-ID: 132804  Cd Length: 123  Bit Score: 41.68  E-value: 1.34e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039745905  54 RRYSDFDLLNNSL----QITGLSLP-------LPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd06894    42 RRYSDFEWLRSELerdsKIVVPPLPgkalkrqLPFRGDDGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFL 118
PX_PI3K_C2 cd06883
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The ...
29-121 1.43e-04

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.


Pssm-ID: 132793  Cd Length: 109  Bit Score: 41.19  E-value: 1.43e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  29 SLQSHTEYIIRVQRGISAENSWqIVRRYSDFDLLNNSLQITGLSLPLPP---KKLIGNMDREFIAE-RQRGLQNYL-NVI 103
Cdd:cd06883    12 SPEKYYIYVVKVTRENQTEPSF-VFRTFEEFQELHNKLSLLFPSLKLPSfpaRVVLGRSHIKQVAErRKIELNSYLkSLF 90
                          90
                  ....*....|....*...
gi 1039745905 104 MANHVLSNCELLKKFLDP 121
Cdd:cd06883    91 NASPEVAESDLVYTFFHP 108
PX_SNX9_18_like cd06862
The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; The PX domain is ...
51-119 1.73e-04

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.


Pssm-ID: 132772  Cd Length: 125  Bit Score: 41.53  E-value: 1.73e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039745905  51 QIVRRYSDFDLLNNSL--QITGLSLP-LPPKKLIGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd06862    33 TVSRRYKHFDWLYERLveKYSCIAIPpLPEKQVTGRFEEDFIEKRRERLELWMNRLARHPVLSQSEVFRHFL 104
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
206-351 2.30e-04

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 43.14  E-value: 2.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 206 HPYIYRVTFATASESSA---LLIRAFNEKGTLKDLIYKAKPKDPFLKKYCnpkktqglelqqiktYGRQILEALKFLHDK 282
Cdd:cd13979    58 HENIVRVLAAETGTDFAslgLIIMEYCGNGTLQQLIYEGSEPLPLAHRIL---------------ISLDIARALRFCHSH 122
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 283 GFPYGHLHAANVMLDGN-TCRLLDLENS-LLGLPSFYRSYFTQFR-----------KINTL-ESVDVHCFGHLLYEMTYG 348
Cdd:cd13979   123 GIVHLDVKPANILISEQgVCKLCDFGCSvKLGEGNEVGTPRSHIGgtytyrapellKGERVtPKADIYSFGITLWQMLTR 202

                  ...
gi 1039745905 349 RPP 351
Cdd:cd13979   203 ELP 205
PX_SNX30 cd07283
The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; The PX domain is a ...
50-119 2.94e-04

The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.


Pssm-ID: 132816  Cd Length: 116  Bit Score: 40.45  E-value: 2.94e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039745905  50 WQIVRRYSDFDLLNNSL---QITGLSLPLPPKKLI-GNMDR---EFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd07283    37 YSVRRRYQDFDWLRNKLeesQPTHLIPPLPEKFVVkGVVDRfseEFVETRRKALDKFLKRIADHPVLSFNEHFNVFL 113
PX_SNX19_like_plant cd06872
The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; ...
20-106 3.04e-04

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132782  Cd Length: 107  Bit Score: 40.20  E-value: 3.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  20 LTAAVEASQSlQSHTEYIIRVQrgiSAEN-SWQIVRRYSDFDLLNNSLQ-ITGLSLPLPPKKLIG-NMDREFIAERQRGL 96
Cdd:cd06872     6 LGAEIVKSGS-KSFAVYSVAVT---DNENeTWVVKRRFRNFETLHRRLKeVPKYNLELPPKRFLSsSLDGAFIEERCKLL 81
                          90
                  ....*....|
gi 1039745905  97 QNYLNVIMAN 106
Cdd:cd06872    82 DKYLKDLLVI 91
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
260-351 3.57e-04

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 42.60  E-value: 3.57e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 260 LELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGNT-CRLLDL------------ENSLLGLPSFYRSYFTQFRK 326
Cdd:cd05619   103 FDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGhIKIADFgmckenmlgdakTSTFCGTPDYIAPEILLGQK 182
                          90       100
                  ....*....|....*....|....*
gi 1039745905 327 INTleSVDVHCFGHLLYEMTYGRPP 351
Cdd:cd05619   183 YNT--SVDWWSFGVLLYEMLIGQSP 205
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
268-351 4.06e-04

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 42.68  E-value: 4.06e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 268 YGRQILEALKFLHDKGFPYGHLHAANVMLDGN---------TCR--LLD--LENSLLGLPSFYRSYFTQFRKINtlESVD 334
Cdd:cd05616   106 YAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEghikiadfgMCKenIWDgvTTKTFCGTPDYIAPEIIAYQPYG--KSVD 183
                          90
                  ....*....|....*..
gi 1039745905 335 VHCFGHLLYEMTYGRPP 351
Cdd:cd05616   184 WWAFGVLLYEMLAGQAP 200
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
178-353 4.15e-04

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 42.37  E-value: 4.15e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 178 LSWADLGPDKY--LSDKDFQCLIKLLPSCVHPYIYRvtFATASESSA------LLIRAFNEKGTLKDLIYKAKPKDPflk 249
Cdd:cd14032    29 VAWCELQDRKLtkVERQRFKEEAEMLKGLQHPNIVR--FYDFWESCAkgkrciVLVTELMTSGTLKTYLKRFKVMKP--- 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 250 kycnpkktqglelQQIKTYGRQILEALKFLHDKGFPYGH--LHAANVMLDGNT--CRLLDLENSLLGLPSFYRSYF---- 321
Cdd:cd14032   104 -------------KVLRSWCRQILKGLLFLHTRTPPIIHrdLKCDNIFITGPTgsVKIGDLGLATLKRASFAKSVIgtpe 170
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1039745905 322 ---TQFRKINTLESVDVHCFGHLLYEMTYGRPPDS 353
Cdd:cd14032   171 fmaPEMYEEHYDESVDVYAFGMCMLEMATSEYPYS 205
PX_UP1_plant cd06879
The phosphoinositide binding Phox Homology domain of uncharacterized plant proteins; The PX ...
6-120 6.71e-04

The phosphoinositide binding Phox Homology domain of uncharacterized plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132789  Cd Length: 138  Bit Score: 40.00  E-value: 6.71e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905   6 KPPAGKVLLDDTVPLTAAVEASQSLQSHTEYIIRVQRGISAENSWQ----IVRRYSDFDLLNNSLQIT----GLSlPLPP 77
Cdd:cd06879    15 KESDGKAINPKVGNMSVVYSEYQPLNNAVDKFYRVQVGVQSPEGITtmrgVLRRFNDFLKLHTDLKKLfpkkKLP-AAPP 93
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1039745905  78 KKLIGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFLD 120
Cdd:cd06879    94 KGLLRMKNRALLEERRHSLEEWMGKLLSDIDLSRSVPVASFLE 136
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
198-353 6.99e-04

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 41.53  E-value: 6.99e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIYRvtFATASESSA------LLIRAFNEKGTLKDliykakpkdpFLKKYcnpkktQGLELQQIKTYGRQ 271
Cdd:cd14033    51 VEMLKGLQHPNIVR--FYDSWKSTVrghkciILVTELMTSGTLKT----------YLKRF------REMKLKLLQRWSRQ 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 272 ILEALKFLHDKGFPYGH--LHAANVMLDGNT--CRLLDLENSLLGLPSFYRSYF-------TQFRKINTLESVDVHCFGH 340
Cdd:cd14033   113 ILKGLHFLHSRCPPILHrdLKCDNIFITGPTgsVKIGDLGLATLKRASFAKSVIgtpefmaPEMYEEKYDEAVDVYAFGM 192
                         170
                  ....*....|...
gi 1039745905 341 LLYEMTYGRPPDS 353
Cdd:cd14033   193 CILEMATSEYPYS 205
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
247-357 8.27e-04

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 41.07  E-value: 8.27e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 247 FLKKYcnpkkTQGLELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGNTC--RLLDL---------ENSLLGLPS 315
Cdd:cd05118    90 LIKDY-----PRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGqlKLADFglarsftspPYTPYVATR 164
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1039745905 316 FYRSYFTQFRKINTLESVDVHCFGHLLYEMTYGRP--PDSVPVD 357
Cdd:cd05118   165 WYRAPEVLLGAKPYGSSIDIWSLGCILAELLTGRPlfPGDSEVD 208
PX_SNX21 cd07301
The phosphoinositide binding Phox Homology domain of Sorting Nexin 21; The PX domain is a ...
51-100 1.19e-03

The phosphoinositide binding Phox Homology domain of Sorting Nexin 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.


Pssm-ID: 132834  Cd Length: 112  Bit Score: 38.63  E-value: 1.19e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039745905  51 QIVRRYSDFDLLNNSLQ------ITGLSLPLppKKLIGNMDREFIAERQRGLQNYL 100
Cdd:cd07301    37 YISRRYSDFERLHRRLRrlfggeMAGVSFPR--KRLRKNFTAETIAKRSRAFEQFL 90
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
178-353 1.23e-03

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 40.86  E-value: 1.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 178 LSWADLgPDKYLSDKD---FQCLIKLLPSCVHPYIYRvtFATASES------SALLIRAFNEKGTLKDLIYKAKPKDPfl 248
Cdd:cd14031    38 VAWCEL-QDRKLTKAEqqrFKEEAEMLKGLQHPNIVR--FYDSWESvlkgkkCIVLVTELMTSGTLKTYLKRFKVMKP-- 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 249 kkycnpkktqglelQQIKTYGRQILEALKFLHDKGFPYGH--LHAANVMLDGNT--CRLLDL----------ENSLLGLP 314
Cdd:cd14031   113 --------------KVLRSWCRQILKGLQFLHTRTPPIIHrdLKCDNIFITGPTgsVKIGDLglatlmrtsfAKSVIGTP 178
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1039745905 315 SF-----YRSYFTqfrkintlESVDVHCFGHLLYEMTYGRPPDS 353
Cdd:cd14031   179 EFmapemYEEHYD--------ESVDVYAFGMCMLEMATSEYPYS 214
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
198-351 1.34e-03

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 40.52  E-value: 1.34e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYI--YRVTFAtasESSALLI-RAFNEKGTLKDLIYKAKPKDPFLKKycnpkktqglelQQIKTYGRQILE 274
Cdd:cd08215    50 VKLLSKLKHPNIvkYYESFE---ENGKLCIvMEYADGGDLAQKIKKQKKKGQPFPE------------EQILDWFVQICL 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 275 ALKFLHDKGFpyghLH----AANVMLD-GNTCRL------------LDLENSLLGLPsFY--------RSYftqfrkiNt 329
Cdd:cd08215   115 ALKYLHSRKI----LHrdlkTQNIFLTkDGVVKLgdfgiskvlestTDLAKTVVGTP-YYlspelcenKPY-------N- 181
                         170       180
                  ....*....|....*....|..
gi 1039745905 330 lESVDVHCFGHLLYEMTYGRPP 351
Cdd:cd08215   182 -YKSDIWALGCVLYELCTLKHP 202
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
265-351 1.61e-03

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 40.35  E-value: 1.61e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 265 IKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGN----------TCRLLDLENSLLGLPS---FYRSYFTQFRKINT-- 329
Cdd:cd14010    96 VRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNgtlklsdfglARREGEILKELFGQFSdegNVNKVSKKQAKRGTpy 175
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039745905 330 -----LESVDVHCF-------GHLLYEMTYGRPP 351
Cdd:cd14010   176 ymapeLFQGGVHSFasdlwalGCVLYEMFTGKPP 209
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
268-351 1.93e-03

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 40.46  E-value: 1.93e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 268 YGRQILEALKFLHDKGFPYGHLHAANVMLD----------GNTCRLLDLENSLLGLPSFYRSYFTQFRKINTleSVDVHC 337
Cdd:cd14209   106 YAAQIVLAFEYLHSLDLIYRDLKPENLLIDqqgyikvtdfGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNK--AVDWWA 183
                          90
                  ....*....|....
gi 1039745905 338 FGHLLYEMTYGRPP 351
Cdd:cd14209   184 LGVLIYEMAAGYPP 197
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
198-368 2.08e-03

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 39.94  E-value: 2.08e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 198 IKLLPSCVHPYIYRVTFATASESSALLIRAFNEKGTLKDLIYKAKPkdpflkkycnpkktqgLELQQIKTYGRQILEALK 277
Cdd:cd14161    53 IEIMSSLNHPHIISVYEVFENSSKIVIVMEYASRGDLYDYISERQR----------------LSELEARHFFRQIVSAVH 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 278 FLHDKGFPYGHLHAANVMLDGNTcrllDLENSLLGLPSFYrsyftqfrkiNTLESVDVHCfGHLLY---EMTYGRPPDSV 354
Cdd:cd14161   117 YCHANGIVHRDLKLENILLDANG----NIKIADFGLSNLY----------NQDKFLQTYC-GSPLYaspEIVNGRPYIGP 181
                         170
                  ....*....|....
gi 1039745905 355 PVDSFppasSLAVV 368
Cdd:cd14161   182 EVDSW----SLGVL 191
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
268-416 2.21e-03

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 40.17  E-value: 2.21e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 268 YGRQILEALKFLHDKGFPYGHLHAANVMLDGNT-CRLLD------------LENSLLGLPSFYRSYFTQfrKINTLESVD 334
Cdd:cd05591   101 YAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGhCKLADfgmckegilngkTTTTFCGTPDYIAPEILQ--ELEYGPSVD 178
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 335 VHCFGHLLYEMTYGRPP----------DSVPVDS--FPPASSLAVVAVLESTLSCEA-----CKNGMPTVSRLLQMPLFS 397
Cdd:cd05591   179 WWALGVLMYEMMAGQPPfeadneddlfESILHDDvlYPVWLSKEAVSILKAFMTKNPakrlgCVASQGGEDAIRQHPFFR 258
                         170
                  ....*....|....*....
gi 1039745905 398 DVLLTTSEKPQFKIPTKLK 416
Cdd:cd05591   259 EIDWEALEQRKVKPPFKPK 277
PX_Grd19 cd07295
The phosphoinositide binding Phox Homology domain of fungal Grd19; The PX domain is a ...
54-124 2.69e-03

The phosphoinositide binding Phox Homology domain of fungal Grd19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.


Pssm-ID: 132828  Cd Length: 116  Bit Score: 37.86  E-value: 2.69e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039745905  54 RRYSDFDLLNNSL--QITGLSLP-LPPKKLIGNMDREFIAERQRGLQNYLNVImANHVL--SNCELLKKFLDPNNY 124
Cdd:cd07295    42 RRYSDFEYFRDILerESPRVMIPpLPGKIFTNRFSDEVIEERRQGLETFLQSV-AGHPLlqTGSKVLAAFLQDPKF 116
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
266-355 2.85e-03

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 39.80  E-value: 2.85e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 266 KTYGRQILEALKFLHDKGFPYGHLHAANVMLD----------GNTCRLLDLENSLLGLPSFYRSYFTQFRKINtlESVDV 335
Cdd:PTZ00263  121 KFYHAELVLAFEYLHSKDIIYRDLKPENLLLDnkghvkvtdfGFAKKVPDRTFTLCGTPEYLAPEVIQSKGHG--KAVDW 198
                          90       100
                  ....*....|....*....|..
gi 1039745905 336 HCFGHLLYEMTYGRPP--DSVP 355
Cdd:PTZ00263  199 WTMGVLLYEFIAGYPPffDDTP 220
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
268-351 2.86e-03

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 39.73  E-value: 2.86e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 268 YGRQILEALKFLHDKGFPYGHLHAANVMLD----------GNTCRLLDLENSLLGLPSFYRSYFTQFRKINTleSVDVHC 337
Cdd:cd05612   106 YASEIVCALEYLHSKEIVYRDLKPENILLDkeghikltdfGFAKKLRDRTWTLCGTPEYLAPEVIQSKGHNK--AVDWWA 183
                          90
                  ....*....|....
gi 1039745905 338 FGHLLYEMTYGRPP 351
Cdd:cd05612   184 LGILIYEMLVGYPP 197
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
266-375 3.21e-03

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 39.56  E-value: 3.21e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 266 KTYGRQILEALKFLHDKGFPYGHLHAANVMLDGNTCRLL-------------DLENSLLGLPSFYRSYFtqFRKINTLES 332
Cdd:cd05604   100 RFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLtdfglckegisnsDTTTTFCGTPEYLAPEV--IRKQPYDNT 177
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039745905 333 VDVHCFGHLLYEMTYGRPP----------DSV---PVdSFPPASSLAVVAVLESTL 375
Cdd:cd05604   178 VDWWCLGSVLYEMLYGLPPfycrdtaemyENIlhkPL-VLRPGISLTAWSILEELL 232
PX_SNX19 cd06893
The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; The PX domain is a ...
51-119 3.55e-03

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.


Pssm-ID: 132803 [Multi-domain]  Cd Length: 132  Bit Score: 37.91  E-value: 3.55e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039745905  51 QIVRRYSDF----DLLNNSLQITGLSLPLPPKKL-----IGNMDREFIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd06893    52 TVNRRFREFltlqTRLEENPKFRKIMNVKGPPKRlfdlpFGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEFL 129
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
268-351 3.70e-03

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 39.60  E-value: 3.70e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 268 YGRQILEALKFLHDKGFPYGHLHAANVMLDGN---------TCRLLDLEN----SLLGLPSFYRSYFTQFRKINtlESVD 334
Cdd:cd05615   116 YAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEghikiadfgMCKEHMVEGvttrTFCGTPDYIAPEIIAYQPYG--RSVD 193
                          90
                  ....*....|....*..
gi 1039745905 335 VHCFGHLLYEMTYGRPP 351
Cdd:cd05615   194 WWAYGVLLYEMLAGQPP 210
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
178-353 3.79e-03

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 39.26  E-value: 3.79e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 178 LSWADLgPDKYLSDKD---FQCLIKLLPSCVHPYIYRvtFATASESSA------LLIRAFNEKGTLKDliykakpkdpFL 248
Cdd:cd14030    53 VAWCEL-QDRKLSKSErqrFKEEAGMLKGLQHPNIVR--FYDSWESTVkgkkciVLVTELMTSGTLKT----------YL 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905 249 KKYcnpkktQGLELQQIKTYGRQILEALKFLHDKGFPYGH--LHAANVMLDGNT--CRLLDLENSLLGLPSFYRSYF--- 321
Cdd:cd14030   120 KRF------KVMKIKVLRSWCRQILKGLQFLHTRTPPIIHrdLKCDNIFITGPTgsVKIGDLGLATLKRASFAKSVIgtp 193
                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1039745905 322 ----TQFRKINTLESVDVHCFGHLLYEMTYGRPPDS 353
Cdd:cd14030   194 efmaPEMYEEKYDESVDVYAFGMCMLEMATSEYPYS 229
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
260-299 5.02e-03

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 39.22  E-value: 5.02e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1039745905 260 LELQQIKTYGRQILEALKFLHDKGFPYGHLHAANVMLDGN 299
Cdd:cd07866   112 LTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQ 151
PX_HS1BP3 cd06868
The phosphoinositide binding Phox Homology domain of HS1BP3; The PX domain is a ...
14-119 5.82e-03

The phosphoinositide binding Phox Homology domain of HS1BP3; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


Pssm-ID: 132778  Cd Length: 120  Bit Score: 37.00  E-value: 5.82e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039745905  14 LDDTVPLTAAVeASQSLQSHTEYIIRVQRGISAENS----------WQIVRRYSDFDLLNNSL--QITGLSLPLPPKK-- 79
Cdd:cd06868     2 LDLTVPEYQEI-RGKTSSGHVLYQIVVVTRLAAFKSakhkeedvvqFMVSKKYSEFEELYKKLseKYPGTILPPLPRKal 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039745905  80 LIGNMDrefIAERQRGLQNYLNVIMANHVLSNCELLKKFL 119
Cdd:cd06868    81 FVSESD---IRERRAAFNDFMRFISKDEKLANCPELLEFL 117
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
248-299 7.91e-03

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 38.23  E-value: 7.91e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039745905 248 LKKYCNpKKTQGLELQQIKTYGRQILEALKFLHDKGFpyghLH----AANVMLDGN 299
Cdd:cd07829    84 LKKYLD-KRPGPLPPNLIKSIMYQLLRGLAYCHSHRI----LHrdlkPQNLLINRD 134
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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