N-terminal conserved domain of Nudc; The N-terminus of nuclear distribution gene C homolog (NUDC) proteins contains a highly conserved region consisting of a predicted three helix bundle. In the human homolog this segment has been targeted for structure determination by the Joint Center for Structural Genomics. NUDC forms a complex with other NUD proteins and is involved in several cellular division activities. Recently it was shown that NUDC regulates platelet-activating factor (PAF) acetylhydrolase with PAF being a pro-inflammatory secondary lipidic messenger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386771288    7 KFDNILLAVAeKHHGGVPEFLGTLASFLRRKTDFF---------TGAKQTEWEKLLLDVFN 58
Cdd:pfam14050   1 KHDNLLLGIL-QEEGGIEDFLDAFFGFLYRRTDFYhvmldpddkMGFPPGVAEKLVLKAFR 60

CS domain; The CS and CHORD (pfam04968) are fused into a single polypeptide chain in metazoans but are found in separate proteins in plants; this is thought to be indicative of an interaction between CS and CHORD. It has been suggested that the CS domain is a binding module for HSP90, implying that CS domain-containing proteins are involved in recruiting heat shock proteins to multiprotein assemblies. Two CS domains are found at the N-terminus of Ubiquitin carboxyl-terminal hydrolase 19 (USP19), these domains may play a role in the interaction of USP19 with cellular inhibitor of apoptosis 2.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386771288  171 ENYTWTQTLEEVELKIPFNLTfGLRARDLVISIGKKSLKVGIKGQTPIIDGELCGEVKTEESVWVLqDSKTVMITLDK 248
Cdd:pfam04969   1 PRYDWYQTLDEVTITIPVKGA-GIKKKDVKVNIKPRSLKVKIKGGYELIDGELFHPIDPEESSWTI-EGKKVEITLKK 76

p23_like domain of NUD (nuclear distribution) C and similar proteins. Aspergillus nidulas (An) NUDC is needed for nuclear movement. AnNUDC is localized at the hyphal cortex, and binds NUDF at spindle pole bodies (SPBs) and in the cytoplasm at different stages in the cell cycle. At the SPBs it is part of the dynein molecular motor/NUDF complex that regulates microtubule dynamics. Mammalian(m) NUDC associates both with the dynein complex and also with an anti-inflammatory enzyme, platelet activating factor acetylhydrolase I, PAF-AH(I) complex, through binding mNUDF, the regulatory beta subunit of PAF-AH(I). mNUDC is important for cell proliferation both in normal and tumor tissues. Its expression is elevated in various cell types undergoing mitosis or stimulated to proliferate, with high expression levels observed in leukemic cells and tumors. For a leukemic cell line, human NUDC was shown to activate the thrombopoietin (TPO) receptor (Mpl) by binding to its extracellular domain, and promoting cell proliferation and differentiation. This group also includes the human broadly immunogenic tumor associated antigen, CML66, which is highly expressed in a variety of solid tumors and in leukemias. In normal tissues high expression of CML66 is limited to testis and heart.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386771288 173 YTWTQTLEEVELKIPFNLtfGLRARDLVISIGKKSLKVGIKGQTPIIDGELCGEVKTEESVWVLQDSKTVMITLDKINKM 252
Cdd:cd06467    1 YSWTQTLDEVTVTIPLPE--GTKSKDVKVEITPKHLKVGVKGGEPLLDGELYAKVKVDESTWTLEDGKLLEITLEKRNEG 78

                 ....*..
gi 386771288 253 NWWSRLV 259
Cdd:cd06467   79 EWWPSLV 85

Proteins containing this p23_like domain include p23 and its Saccharomyces cerevisiae (Sc) homolog Sba1. Both are co-chaperones for the heat shock protein (Hsp) 90. p23 binds Hsp90 and participates in the folding of a number of Hsp90 clients, including the progesterone receptor. p23 also has a passive chaperoning activity and in addition may participate in prostaglandin synthesis. Both p23 and Sba1p can regulate telomerase activity. This group includes domains similar to the C-terminal CHORD-SGT1 (CS) domain of suppressor of G2 allele of Skp1 (Sgt1). Sgt1 interacts with multiple protein complexes and has the features of a co-chaperone. Human (h) Sgt1 interacts with both Hsp70 and Hsp90, and has been shown to bind Hsp90 through its CS domain. Saccharomyces cerevisiae (Sc) Sgt1 is a subunit of both core kinetochore and SCF (Skp1-Cul1-F-box) ubiquitin ligase complexes. Sgt1 is required for pathogen resistance in plants. This group also includes the p23_like domains of human butyrate-induced transcript 1 (hB-ind1), NUD (nuclear distribution) C, Melusin, and NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR). hB-ind1 plays a role in the signaling pathway mediated by the small GTPase Rac1, NUDC is needed for nuclear movement, Melusin interacts with two splice variants of beta1 integrin, and NCB5OR plays a part in maintaining viable pancreatic beta cells.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386771288 175 WTQTLEEVELKIPFNltfGLRARDLVISIGKKSLKVGIK---GQTPIIDGELCGEVKTEESVWVLqDSKTVMITLDKINK 251
Cdd:cd06463    1 WYQTLDEVTITIPLK---DVTKKDVKVEFTPKSLTVSVKgggGKEYLLEGELFGPIDPEESKWTV-EDRKIEITLKKKEP 76

                 ....*...
gi 386771288 252 MNWWSRLV 259
Cdd:cd06463   77 GEWWPRLE 84

p23-like NUD (nuclear distribution) C-like found in human NUDC domain-containing protein 2 (NUDCD2) and similar proteins. Little is known about the function of the proteins in this subgroup.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386771288 175 WTQTLEEVELKIpfNLTFGLRARDLVISIGKKSLKVGIKGQTpIIDGELCGEVKTEESVWVLQDSKTVMITLDKINK--M 252
Cdd:cd06494   10 WYQTMDEVFIEV--NVPPGTRAKDVKCKLGSRDISLAVKGQE-VLKGKLFDSVVADECTWTLEDRKLIRIVLTKSNRdaG 86

                 ....*.
gi 386771288 253 NWWSRL 258
Cdd:cd06494   87 NCWKSL 92

p23_NUDCD1: p23-like NUD (nuclear distribution) C-like domain found in human NUD (nuclear distribution) C domain-containing protein 1, NUDCD1 (also known as CML66), and similar proteins. NUDCD1/CML66 is a broadly immunogenic tumor associated antigen, which is highly expressed in a variety of solid tumors and in leukemias. In normal tissues high expression of NUDCD1/CML66 is limited to testis and heart.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386771288 173 YTWTQTLEEVELKIpfNLTFGLRARDLVISIGKKSLKVGIKGQTPIIDGELCGEVKTEESVWVLQDSKTVMITLDKINKM 252
Cdd:cd06493    1 YYWQQTEEDLTLTI--RLPEDTTKEDIRIKFLPDHISIALKDQAPLLEGKLYSSIDHESSTWIIKENKSLEVSLIKKDEG 78

                 ....*..
gi 386771288 253 NWWSRLV 259
Cdd:cd06493   79 PTWPELV 85