mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70); [Transport and binding proteins, Amino acids, peptides and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1444813235 261 KERGDKHYRAQAWQQAAECYTESI--KRDGVFMTcvmNRAACRLQLGAYKEAAEDCTLALtmlmntpasEVTQDRYRMLM 338
Cdd:TIGR00990 131 KEKGNKAYRNKDFNKAIKLYSKAIecKPDPVYYS---NRAACHNALGDWEKVVEDTTAAL---------ELDPDYSKALN 198

                          90       100
                  ....*....|....*....|....
gi 1444813235 339 aklhaRRGAAHGWLGDLVESATDL 362
Cdd:TIGR00990 199 -----RRANAYDGLGKYADALLDL 217

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1444813235   5 PSFTWDQSDTDVYLTVTLK--GCKKDAVDVFFSSLFVKVNAAPTYLLSL-DLLHAVDATQCSY 64
Cdd:pfam04969   1 PRYDWYQTLDEVTITIPVKgaGIKKKDVKVNIKPRSLKVKIKGGYELIDgELFHPIDPEESSW 63

Tetratricopeptide (TPR) repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1444813235 255 DSPLFWKERGDKHYRAQAWQQAAECYTESIKRDGVFMTCVMNRAACRLQLGAYKEAAEDCTLALTMLMNtpasevtqdry 334
Cdd:COG0457     6 DDAEAYNNLGLAYRRLGRYEEAIEDYEKALELDPDDAEALYNLGLAYLRLGRYEEALADYEQALELDPD----------- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1444813235 335 rmlMAKLHARRGAAHGWLGDLVESATDLRMAVAYSTDeDDEVRADLARVealaasrglvlrdapdptdgqmvaaagLYYK 414
Cdd:COG0457    75 ---DAEALNNLGLALQALGRYEEALEDYDKALELDPD-DAEALYNLGLA---------------------------LLEL 123

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1444813235 415 QQYGEAAAVYSAVLEAQPLHVPARANRAAARLLLRDFKGALADCEELIQFCGEVAAALQDPELR 478
Cdd:COG0457   124 GRYDEAIEAYERALELDPDDADALYNLGIALEKLGRYEEALELLEKLEAAALAALLAAALGEAA 187

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1444813235   9 WDQSDTDVYLTVTLKGCKKDAVDVFFS--SLFVKVNAA--PTYLLSLDLLHAVDATQCSYAFDGadaSQLSLRLRKREAA 84
Cdd:cd06463     1 WYQTLDEVTITIPLKDVTKKDVKVEFTpkSLTVSVKGGggKEYLLEGELFGPIDPEESKWTVED---RKIEITLKKKEPG 77

                  ....*..
gi 1444813235  85 VVWPALT 91
Cdd:cd06463    78 EWWPRLE 84

p23_like domain similar to the C-terminal CHORD-SGT1 (CS) domain of Sgt1 (suppressor of G2 allele of Skp1). Sgt1 interacts with multiple protein complexes and has the features of a cochaperone. 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. ScSgt1 is needed for the G1/S and G2/M cell-cycle transitions, and for assembly of the core kinetochore complex (CBF3) via activation of Ctf13, the F-box protein. Binding of Hsp82 (a yeast Hsp90 homologue) to ScSgt1, promotes the binding of Sgt1 to Skp1 and of Skp1 to Ctf13. Some proteins in this group have an SGT1-specific (SGS) domain at the extreme C-terminus. The ScSgt1-SGS domain binds adenylate cyclase. The hSgt1-SGS domain interacts with some S100 family proteins, and studies suggest that the interaction of hSgt1 with Hsp90 and Hsp70 may be regulated by S100A6 in a Ca2+ dependent fashion. This group also includes the p23_like domains of Melusin and NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR). Melusin is a vertebrate protein which interacts with two splice variants of beta1 integrin, and NCB5OR plays a part in maintaining viable pancreatic beta cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1444813235   9 WDQSDTDVYLTVTLKGCKKDAVDVFFS----SLFVKVNAAPTYLLSLDLLHAVDATQCSYAFDGadaSQLSLRLRKREaA 84
Cdd:cd06466     2 WYQTDTSVTVTIYAKNVDKEDVKVEFNeqslSVSIILPGGSEYQLELDLFGPIDPEQSKVSVLP---TKVEITLKKAE-P 77

                  ....*..
gi 1444813235  85 VVWPALT 91
Cdd:cd06466    78 GSWPSLE 84

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 1444813235   7 FTWDQSDTDVYLTVTL-KGCKKDAVDVFFS--SLFVKVNAAPTyLLSLDLLHAVDATQCSYAFDgaDASQLSLRLRKREA 83
Cdd:cd06467     1 YSWTQTLDEVTVTIPLpEGTKSKDVKVEITpkHLKVGVKGGEP-LLDGELYAKVKVDESTWTLE--DGKLLEITLEKRNE 77

                  ....*..
gi 1444813235  84 AVVWPAL 90
Cdd:cd06467    78 GEWWPSL 84

p23_like domain found in human (h) butyrate-induced transcript 1 (B-ind1) and similar proteins. hB-ind1 participates in signaling by the small GTPase Rac1. It binds to Rac1 and enhances different Rac1 effects including activation of nuclear factor (NF) kappaB and activation of c-Jun N-terminal kinase (JNK). hB-ind1 also plays a part in the RNA replication and particle production of Hepatitis C virus (HCV) through its interaction with heat shock protein Hsp90, HCV nonstructural protein 5A (NS5A), and the immunophilin FKBP8. hB-ind1 is upregulated in the outer layer of Chinese hamster V79 cells grown as multicell spheroids, versus in the same cells grown as monolayers. This group includes the Saccharomyces cerevisiae Sba1, a co-chaperone of the Hsp90. Sba1 has been shown to be is required for telomere length maintenance, and may modulate telomerase DNA-binding activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1444813235   5 PSFTWDQSDTDVYLTVTLKGCKKDAVDVFFSSLFVKVNAAP---TYLLSLDLLHAVDATQCSYAFDGadaSQLSLRLRKR 81
Cdd:cd06465     1 PPVLWAQRSDVVYLTIELPDAKDPKIKLEPTSLSFKAKGGGggkKYEFDLEFYKEIDPEESKYKVTG---RQIEFVLRKK 77

                          90
                  ....*....|
gi 1444813235  82 EAAVVWPALT 91
Cdd:cd06465    78 EAGEYWPRLT 87

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 1444813235   6 SFTWDQSDTDVYLTVTLKG---CKKDAVDVFF--SSLFVKVNAAPT--YLLSL-DLLHAVDATQCSYAfdgADASQLSLR 77
Cdd:cd06468     3 KYAWDQSDKFVKIYITLKGvhqLPKENIQVEFteRSFELKVHDLNGknYRFTInRLLKKIDPEKSSFK---VKTDRIVIT 79

                          90
                  ....*....|....
gi 1444813235  78 LRKREAAvVWPALT 91
Cdd:cd06468    80 LAKKKEK-KWESLT 92