alpha-crystallin domain (ACD) found in alpha-crystallin-type small heat shock proteins, and a similar domain found in p23 (a cochaperone for Hsp90) and in other p23-like proteins.; The alpha-crystallin-Hsps_p23-like superfamily includes the alpha-crystallin domain (ACD) of alpha-crystallin-type small heat shock proteins (sHsps) and a similar domain found in p23-like proteins. sHsps are small stress induced proteins with monomeric masses between 12-43 kDa, whose common feature is this ACD. sHsps are generally active as large oligomers consisting of multiple subunits, and are believed to be ATP-independent chaperones that prevent aggregation and are important in refolding in combination with other Hsps. p23 is a cochaperone of the Hsp90 chaperoning pathway. It binds Hsp90 and participates in the folding of a number of Hsp90 clients including the progesterone receptor. p23 also has a passive chaperoning activity. p23 in addition may act as the cytosolic prostaglandin E2 synthase. Included in this superfamily is the p23-like C-terminal CHORD-SGT1 (CS) domain of suppressor of G2 allele of Skp1 (Sgt1) and 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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225427143  64 YEFSDASSEMELRLQLGGGgtLSSRDIFVDAEDSSLKIGVKQSGSFITlveiNKLYEKIKSSETIWYI-DEDQLVVNLKK 142
Cdd:cd06467    1 YSWTQTLDEVTVTIPLPEG--TKSKDVKVEITPKHLKVGVKGGEPLLD----GELYAKVKVDESTWTLeDGKLLEITLEK 74

                         90
                 ....*....|.
gi 225427143 143 QDPDLKWPDIV 153
Cdd:cd06467   75 RNEGEWWPSLV 85

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 225427143  64 YEFSDASSEMELRLQLGGGgtLSSRDIFVDAEDSSLKIGVKQSGSFITlveiNKLYEKIKSSETIWYI-DEDQLVVNLKK 142
Cdd:cd06467    1 YSWTQTLDEVTVTIPLPEG--TKSKDVKVEITPKHLKVGVKGGEPLLD----GELYAKVKVDESTWTLeDGKLLEITLEK 74

                         90
                 ....*....|.
gi 225427143 143 QDPDLKWPDIV 153
Cdd:cd06467   75 RNEGEWWPSLV 85

shikimate kinase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225427143 167 LKGTSIYIVGDSTEINDKVARELAVGLGYTPLNTKELLETFAKQSIDSWVTADGSESV-AEAESAVLENLSSHVRAVIAT 245
Cdd:PLN02199 100 LNGRSMYLVGMMGSGKTTVGKLMSKVLGYTFFDCDTLIEQAMNGTSVAEIFVHHGENFfRGKETDALKKLSSRYQVVVST 179

                         90       100
                 ....*....|....*....|....*
gi 225427143 246 LGglhGAARRADKWRHLYAGFTVWL 270
Cdd:PLN02199 180 GG---GAVIRPINWKYMHKGISIWL 201

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225427143   63 NYEFSDASSEMELRLQLGGGGTlSSRDIFVDAEDSSLKIGVKQSGSFItlveINKLYEKIKSSETIWYIDEDQLVVNLKK 142
Cdd:pfam04969   2 RYDWYQTLDEVTITIPVKGAGI-KKKDVKVNIKPRSLKVKIKGGYELI----DGELFHPIDPEESSWTIEGKKVEITLKK 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 225427143  64 YEFSDASSEMELRLQLGGGgtLSSRDIFVDAEDSSLKIGVKQSGSFITlveiNKLYEKIKSSETIWYI-DEDQLVVNLKK 142
Cdd:cd06467    1 YSWTQTLDEVTVTIPLPEG--TKSKDVKVEITPKHLKVGVKGGEPLLD----GELYAKVKVDESTWTLeDGKLLEITLEK 74

                         90
                 ....*....|.
gi 225427143 143 QDPDLKWPDIV 153
Cdd:cd06467   75 RNEGEWWPSLV 85

Shikimate kinase (SK) is the fifth enzyme in the shikimate pathway, a seven-step biosynthetic pathway which converts erythrose-4-phosphate to chorismic acid, found in bacteria, fungi and plants. Chorismic acid is a important intermediate in the synthesis of aromatic compounds, such as aromatic amino acids, p-aminobenzoic acid, folate and ubiquinone. Shikimate kinase catalyses the phosphorylation of the 3-hydroxyl group of shikimic acid using ATP.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225427143 171 SIYIVG-----DSTeindkVARELAVGLGYTPLNTKELLETFAKQSIDSWVTADGSESVAEAESAVLENLSSHVRAVIAT 245
Cdd:cd00464    1 NIVLIGmmgagKTT-----VGRLLAKALGLPFVDLDELIEQRAGMSIPEIFAEEGEEGFRELEREVLLLLLTKENAVIAT 75

                         90       100
                 ....*....|....*....|....*.
gi 225427143 246 lGGlhGA-ARRADKWRHLYAGFTVWL 270
Cdd:cd00464   76 -GG--GAvLREENRRLLLENGIVVWL 98

Shikimate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225427143  175 VGDSTeindkVARELAVGLGYTPLNTKELLETFAKQSIDSWVTADGSESVAEAESAVLENLSSHVRAVIATlGGlhGAAR 254
Cdd:pfam01202   3 AGKST-----IGRLLAKALGLPFIDTDEEIEKRTGMSIAEIFEEEGEEGFRRLESEVLKELLAEHGLVIAT-GG--GAVL 74

                          90
                  ....*....|....*..
gi 225427143  255 RADKWRHLYA-GFTVWL 270
Cdd:pfam01202  75 SEENRDLLKErGIVIYL 91

p23_like domain found in proteins similar to Calcyclin-Binding Protein(CacyBP)/Siah-1-interacting protein (SIP). CacyBP/SIP interacts with S100A6 (calcyclin), with some other members of the S100 family, with tubulin, and with Siah-1 and Skp-1. The latter two are components of the ubiquitin ligase that regulates beta-catenin degradation. The beta-catenin gene is an oncogene participating in tumorigenesis in many different cancers. Overexpression of CacyBP/SIP, in part through its effect on the expression of beta-catenin, inhibits the proliferation, tumorigenicity, and invasion of gastric cancer cells. CacyBP/SIP is abundant in neurons and neuroblastoma NB2a cells. An extensive re-organization of microtubules accompanies the differentiation of NB2a cells. CacyBP/SIP may contribute to NB2a cell differentiation through binding to and increasing the oligomerization of tubulin. CacyBP/SIP is also implicated in differentiation of erythroid cells, rat neonatal cardiomyocytes, in mouse endometrial events, and in thymocyte development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225427143  62 SNYEFSDASSEMELRLQLGGGGTLSSRDIFVDAEDSSLKIGVKQ-SGSFITLVeINKLYEKIKSSETIWYIDEDQLVVNL 140
Cdd:cd06468    2 TKYAWDQSDKFVKIYITLKGVHQLPKENIQVEFTERSFELKVHDlNGKNYRFT-INRLLKKIDPEKSSFKVKTDRIVITL 80

                         90
                 ....*....|..
gi 225427143 141 KKQDPDlKWPDI 152
Cdd:cd06468   81 AKKKEK-KWESL 91