ID SPSB4_HUMAN Reviewed; 273 AA. AC Q96A44; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 15-MAR-2017, entry version 123. DE RecName: Full=SPRY domain-containing SOCS box protein 4; DE Short=SSB-4; GN Name=SPSB4; Synonyms=SSB4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Friedel E.J., Nicholson S.E., Nicola N.A., Kile B.T., Hilton D.J.; RT "SOCS box proteins."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION IN AN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, AND INTERACTION RP WITH CUL5; RNF7; ELOB AND ELOC. RX PubMed=15601820; DOI=10.1101/gad.1252404; RA Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., RA Conaway R.C., Conaway J.W., Nakayama K.I.; RT "VHL-box and SOCS-box domains determine binding specificity for Cul2- RT Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases."; RL Genes Dev. 18:3055-3065(2004). RN [5] RP INTERACTION WITH MET. RX PubMed=15713673; DOI=10.1074/jbc.M413897200; RA Wang D., Li Z., Messing E.M., Wu G.; RT "The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with RT MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum RT response element pathway."; RL J. Biol. Chem. 280:16393-16401(2005). CC -!- FUNCTION: Probable substrate recognition component of a SCF-like CC ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein CC ligase complex which mediates the ubiquitination and subsequent CC proteasomal degradation of target proteins. CC {ECO:0000269|PubMed:15601820}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with PARW (By similarity). Probable component CC of the ECS(SPSB4) E3 ubiquitin-protein ligase complex which CC contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB4. Interacts CC with MET. {ECO:0000250, ECO:0000269|PubMed:15601820, CC ECO:0000269|PubMed:15713673}. CC -!- INTERACTION: CC Q15369:TCEB1; NbExp=2; IntAct=EBI-2323233, EBI-301231; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- DOMAIN: The SOCS box domain mediates the interaction with the CC Elongin BC complex, an adapter module in different E3 ubiquitin CC ligase complexes. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the SPSB family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF403029; AAL57348.1; -; mRNA. DR EMBL; AK056367; BAB71165.1; -; mRNA. DR EMBL; BC008324; AAH08324.1; -; mRNA. DR CCDS; CCDS3115.1; -. DR RefSeq; NP_543138.1; NM_080862.2. DR UniGene; Hs.655112; -. DR PDB; 2V24; X-ray; 2.20 A; A=28-233. DR PDBsum; 2V24; -. DR ProteinModelPortal; Q96A44; -. DR SMR; Q96A44; -. DR BioGrid; 124941; 8. DR IntAct; Q96A44; 6. DR STRING; 9606.ENSP00000311609; -. DR iPTMnet; Q96A44; -. DR PhosphoSitePlus; Q96A44; -. DR BioMuta; SPSB4; -. DR DMDM; 74731085; -. DR PaxDb; Q96A44; -. DR PRIDE; Q96A44; -. DR DNASU; 92369; -. DR Ensembl; ENST00000310546; ENSP00000311609; ENSG00000175093. DR GeneID; 92369; -. DR KEGG; hsa:92369; -. DR UCSC; uc003ett.4; human. DR CTD; 92369; -. DR DisGeNET; 92369; -. DR GeneCards; SPSB4; -. DR HGNC; HGNC:30630; SPSB4. DR HPA; HPA073015; -. DR MIM; 611660; gene. DR neXtProt; NX_Q96A44; -. DR OpenTargets; ENSG00000175093; -. DR PharmGKB; PA142670874; -. DR eggNOG; KOG3953; Eukaryota. DR eggNOG; ENOG410XQC1; LUCA. DR GeneTree; ENSGT00390000009402; -. DR HOGENOM; HOG000230524; -. DR HOVERGEN; HBG055793; -. DR InParanoid; Q96A44; -. DR KO; K10343; -. DR OMA; CKNQPGV; -. DR OrthoDB; EOG091G0DF0; -. DR PhylomeDB; Q96A44; -. DR TreeFam; TF312822; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR ChiTaRS; SPSB4; human. DR EvolutionaryTrace; Q96A44; -. DR GenomeRNAi; 92369; -. DR PRO; PR:Q96A44; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; ENSG00000175093; -. DR CleanEx; HS_SPSB4; -. DR ExpressionAtlas; Q96A44; baseline and differential. DR Genevisible; Q96A44; HS. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR013320; ConA-like_dom. DR InterPro; IPR001496; SOCS_box. DR InterPro; IPR003877; SPRY_dom. DR Pfam; PF07525; SOCS_box; 1. DR Pfam; PF00622; SPRY; 1. DR SMART; SM00969; SOCS_box; 1. DR SMART; SM00449; SPRY; 1. DR SUPFAM; SSF158235; SSF158235; 1. DR SUPFAM; SSF49899; SSF49899; 1. DR PROSITE; PS50188; B302_SPRY; 1. DR PROSITE; PS50225; SOCS; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Cytoplasm; Reference proteome; KW Ubl conjugation pathway. FT CHAIN 1 273 SPRY domain-containing SOCS box protein FT 4. FT /FTId=PRO_0000238477. FT DOMAIN 34 233 B30.2/SPRY. {ECO:0000255|PROSITE- FT ProRule:PRU00548}. FT DOMAIN 234 273 SOCS box. {ECO:0000255|PROSITE- FT ProRule:PRU00194}. FT HELIX 37 42 {ECO:0000244|PDB:2V24}. FT HELIX 48 53 {ECO:0000244|PDB:2V24}. FT STRAND 55 61 {ECO:0000244|PDB:2V24}. FT STRAND 65 68 {ECO:0000244|PDB:2V24}. FT STRAND 71 77 {ECO:0000244|PDB:2V24}. FT STRAND 81 90 {ECO:0000244|PDB:2V24}. FT STRAND 93 103 {ECO:0000244|PDB:2V24}. FT HELIX 106 108 {ECO:0000244|PDB:2V24}. FT STRAND 114 118 {ECO:0000244|PDB:2V24}. FT STRAND 125 129 {ECO:0000244|PDB:2V24}. FT STRAND 139 143 {ECO:0000244|PDB:2V24}. FT TURN 144 147 {ECO:0000244|PDB:2V24}. FT STRAND 148 150 {ECO:0000244|PDB:2V24}. FT STRAND 159 162 {ECO:0000244|PDB:2V24}. FT STRAND 175 182 {ECO:0000244|PDB:2V24}. FT TURN 183 186 {ECO:0000244|PDB:2V24}. FT STRAND 187 192 {ECO:0000244|PDB:2V24}. FT STRAND 195 201 {ECO:0000244|PDB:2V24}. FT STRAND 209 215 {ECO:0000244|PDB:2V24}. FT STRAND 217 219 {ECO:0000244|PDB:2V24}. FT STRAND 221 230 {ECO:0000244|PDB:2V24}. SQ SEQUENCE 273 AA; 30179 MW; 234A651A08217489 CRC64; MGQKLSGSLK SVEVREPALR PAKRELRGAE PGRPARLDQL LDMPAAGLAV QLRHAWNPED RSLNVFVKDD DRLTFHRHPV AQSTDGIRGK VGHARGLHAW QINWPARQRG THAVVGVATA RAPLHSVGYT ALVGSDAESW GWDLGRSRLY HDGKNQPGVA YPAFLGPDEA FALPDSLLVV LDMDEGTLSF IVDGQYLGVA FRGLKGKKLY PVVSAVWGHC EVTMRYINGL DPEPLPLMDL CRRSIRSALG RQRLQDISSL PLPQSLKNYL QYQ //