Tetraspanin, extracellular domain or large extracellular loop (LEL), penumbra_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". Human Penumbra exhibits growth-suppressive activity in vitro and has been associated with myeloid malignancies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 114 LIFRNQTIDFLNDNIRRGIENYYDDLDFKNIMDFVQKKFKCCGGEDYRDWSKNQYHDCSAPGPLACGVPYTCCIRNT-TD 192
Cdd:cd03158    1 FIFSNQTIDLLEENIRKAIVHYYDDLDLQNIIDFVQKEFKCCGGDDYRDWSKNMYFNCSSPNPEACGVPYSCCIRAKdQE 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 110347498 193 VVNTMCGYKTIDKERLNAQNIIHVRGCTNAVLIWFMDNY 231
Cdd:cd03158   81 VINTMCGYGVQNLERLEASKLIYTRGCIDAVVLWIEDNL 119

Tetraspanin, extracellular domain or large extracellular loop (LEL), penumbra_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". Human Penumbra exhibits growth-suppressive activity in vitro and has been associated with myeloid malignancies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 114 LIFRNQTIDFLNDNIRRGIENYYDDLDFKNIMDFVQKKFKCCGGEDYRDWSKNQYHDCSAPGPLACGVPYTCCIRNT-TD 192
Cdd:cd03158    1 FIFSNQTIDLLEENIRKAIVHYYDDLDLQNIIDFVQKEFKCCGGDDYRDWSKNMYFNCSSPNPEACGVPYSCCIRAKdQE 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 110347498 193 VVNTMCGYKTIDKERLNAQNIIHVRGCTNAVLIWFMDNY 231
Cdd:cd03158   81 VINTMCGYGVQNLERLEASKLIYTRGCIDAVVLWIEDNL 119

Tetraspanin, extracellular domain or large extracellular loop (LEL), penumbra_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". Human Penumbra exhibits growth-suppressive activity in vitro and has been associated with myeloid malignancies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 114 LIFRNQTIDFLNDNIRRGIENYYDDLDFKNIMDFVQKKFKCCGGEDYRDWSKNQYHDCSAPGPLACGVPYTCCIRNT-TD 192
Cdd:cd03158    1 FIFSNQTIDLLEENIRKAIVHYYDDLDLQNIIDFVQKEFKCCGGDDYRDWSKNMYFNCSSPNPEACGVPYSCCIRAKdQE 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 110347498 193 VVNTMCGYKTIDKERLNAQNIIHVRGCTNAVLIWFMDNY 231
Cdd:cd03158   81 VINTMCGYGVQNLERLEASKLIYTRGCIDAVVLWIEDNL 119

Tetraspanin, extracellular domain or large extracellular loop (LEL), TM4SF9_like subfamily. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". This subfamily contaions transmembrane 4 superfamily 9 (TM4SF9) or Tetraspanin-5 and related proteins. TM4SF9 is strongly expressed witin the central nervous system, and expression levels appear to correlate with differentiation status of particular neurons, hinting at a role in neuronal maturation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 116 FRNQTIDFLNDNIRrgieNYYDDLDFKNIMDFVQKKFKCCGGEDYRDWSKNQYHDCS--APGPLACGVPYTCCIRN-TTD 192
Cdd:cd03159    7 IKDQLTEFLNNNIR----AYRDDIDLQNLIDFLQEYWQCCGARGPDDWNLNIYFNCTdsNPSRERCGVPFSCCVKDpAED 82

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 110347498 193 VVNTMCGYKTIDKERLNAQNIIHVRGCTNAVLIWFMDN 230
Cdd:cd03159   83 VVNTQCGYDVRKKPELELQHHIHTKGCVQAFEKWLQDN 120

Tetraspanin, extracellular domain or large extracellular loop (LEL), CD63 family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". CD63 is present in platelets, neutrophils, and endothelial cells, amongst others. In platelets it associates with the integrin alphaIIBbeta3 and may modulate alphaIIbbeta3-dependent cytoskeletal reorganization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 115 IFRNQTIDFLNDNIRRGIENYYDDLDFKNIMDFVQKKFKCCGGEDYRDWSknqyhdcSAPGPLACGVPYTCCIRNTTDvv 194
Cdd:cd03166    2 VFRDKVMSEFNDSFNQMISNYNKTNDFRKILDRMQKDLKCCGANNYTDWE-------NIPSLDTDSVPDSCCINVTKG-- 72

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 110347498 195 ntmCGyktIDKERLnaqnIIHVRGCTNAVLIWFMDN 230
Cdd:cd03166   73 ---CG---INFDEK----VIHLEGCVTKIEGWLKKN 98

Tetraspanin, extracellular domain or large extracellular loop (LEL), CD151_Like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". CD151strongly associates with integrins, especially alpha3beta1, alpha6beta1, alpha7beta1, and alpha6beta4; it may play roles in cell-cell adhesion, cell migration, platelet aggregation, and angiogenesis. For example, CD151 is is involved in regulation of migration of neutrophils, endothelial cells, and various tumor cell lines; it associates specifically with laminin-binding integrins and strengthens alpha6beta1 integrin-mediated adhesion to laminin-1; CD151 also specifically attenuates adhesion-dependent activation of Ras and correspdonding downstream effects, and is involved in epithelial cell-cell adhesion as a modulator of PKC- and Cdc42-dependent actin cytoskeletal reorganization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 124 LNDNIRRGIENYY---DDLDFKNIMDFVQKKFKCCGGEDYRDWSKNQYHDCSAP-GPLacgVPYTCCIRNTTDvvntmCG 199
Cdd:cd03155   11 LKESLKRTMQENYgqsGEEALTLTVDELQQEFKCCGSNNYTDWQDSEWINSNEAnGRL---VPDSCCKTVVDR-----CG 82

                         90       100
                 ....*....|....*....|.
gi 110347498 200 yktidKERLNAQNIIHV-RGC 219
Cdd:cd03155   83 -----CLRDHPSNIYKVeGGC 98

Tetraspanin, extracellular domain or large extracellular loop (LEL), uroplakin_I_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". Uroplakin Ia and Ib are components of the 16nm protein particles, which are packed hexagonally to form 2D crystals of asymmetric unit membranes, and cover the apical surface of mammalian urothelium, contributing to the urinay bladder's permeability barrier function. Uroplakins Ia and Ib are maturation facilitators. They trigger conformational changes in their single-transmembrane-domain binding partner proteins uroplakin II and IIIa, which in turn may lead to ER-exit, stabilization, and cell-surface expression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 112 VALIFRNQTIDFLNDNIRRGIENYY-DDLDFKNIMDFVQKKFKCCGGEDYRDWSKNQYHDCSAPGPlACGVPYTCCIRNT 190
Cdd:cd03156    1 LALFFKKDLEDSFKNLLKNNYGNYNsTGDAITSTWNRVMIELKCCGVNGPTDFVDSTSFFRQKNEP-NSPYPESCCKRNS 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 110347498 191 TDVVNTMCGYKtidkerLNAQNIIHVRGCTNAVLIWFMDNY 231
Cdd:cd03156   80 NSQIVDLDCPK------LGSPNSYNKKGCYEKLSNPIERYA 114

Tetraspanin, extracellular domain or large extracellular loop (LEL), peripherin_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". Peripherin, or RDS (retinal degradation slow) is a glycoprotein expressed in vertebrate photoreceptors, located at the rim of the disc membranes of the photoreceptor outer segments. RDS is thought to play a major role in folding and stacking of the discs. Mutations in RDS have been linked to hereditary retinal dystrophies, which typically exhibit a wide phenotypic spectrum.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 114 LIFRNQtidfLNDNIRRGIEN---YYDDLD------FKNIMDFVQKKFKCCGGEDYRDWSK-----NQYHDCSAPGP--- 176
Cdd:cd03162    1 FIMRGS----LEESLKTGLKNamkFYKDTDtpgrcfLKKTIDMLQIEFQCCGNNGYRDWFEiqwisNRYLDFSSKEVkdr 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 110347498 177 ---------LACGVPYTC--------CIRNTtdVVNTMCGYKTID-KERLNaqniIHVRGCTNAVLIWFMD 229
Cdd:cd03162   77 iksnvdgryLTDGVPFSCcnpssprpCIQHQ--ITDNSAHYNYDYqTEELN----LWTRGCREALLEYYTS 141

Tetraspanin, extracellular domain or large extracellular loop (LEL), CD37_CD82_Like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". CD37 is a leukocyte-specific protein, and its restricted expression pattern suggests a role in the immune system. A regulatory role in T-cell proliferation has been suggested. CD82 is a metastasis suppressor implicated in biological processes ranging from fusion, adhesion, and migration to apoptosis and alterations of cell morphology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 146 DFVQKKFKCCGGEDYRDWSKNQYHDCSaPGPLacgVPYTCC---IRNTTDVVNT-MCGYKTidkerlNAQNIIHVRGCTN 221
Cdd:cd03160   37 DYVQFQLQCCGWTGPQDWTDNSLIKNS-SEPL---YPCSCCnssATADSPRPSKgFCEAPA------SLDWPVYQEGCME 106

                         90
                 ....*....|
gi 110347498 222 AVLIWFMDNY 231
Cdd:cd03160  107 KLQSWLNENL 116

Tetraspanin, extracellular domain or large extracellular loop (LEL), TM4SF3_like subfamily. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web". This subfamily contaions transmembrane 4 superfamily 3 (TM4SF3) or D6.1a and related proteins. D6.1a associates with alpha6beta4 integrin and supports cell motility, it has been ascribed a role in tumor progression and metastasis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 110347498 110 GIVALIFRNQTIDFLNDNIRRGI-ENYYDDLDFKNIMDFVQKKFKCCGGEDYRDWSKNQYhdcsapgplacgvPYTC-CI 187
Cdd:cd03154    1 GIVGAVYKPKIENELKEKNTKLLsLLGQNAKSVKKSLEKFQKELKCCGLVNGADDWGNDI-------------PASCnCT 67

                         90
                 ....*....|....*....
gi 110347498 188 RNTTDVVNTMCGYKTIDKE 206
Cdd:cd03154   68 TTQSDCVVAYYGGSNVYKE 86