SPSB4_MOUSE
ID SPSB4_MOUSE Reviewed; 273 AA.
AC Q8R5B6; Q8BJI9; Q8VHS8;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=SPRY domain-containing SOCS box protein 4;
DE Short=SSB-4;
GN Name=Spsb4; Synonyms=Ssb4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Friedel E.J., Nicholson S.E., Nicola N.A., Kile B.T., Hilton D.J.;
RT "SOCS box proteins.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Embryonic heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH PAWR AND MET.
RX PubMed=16369487; DOI=10.1038/nsmb1034;
RA Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., Smith B.J.,
RA Babon J.J., Nicola N.A., Norton R.S., Nicholson S.E.;
RT "The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-
RT 4-binding residues.";
RL Nat. Struct. Mol. Biol. 13:77-84(2006).
RN [5]
RP INTERACTION WITH NOS2.
RX PubMed=20603330; DOI=10.1083/jcb.200912087;
RA Kuang Z., Lewis R.S., Curtis J.M., Zhan Y., Saunders B.M., Babon J.J.,
RA Kolesnik T.B., Low A., Masters S.L., Willson T.A., Kedzierski L., Yao S.,
RA Handman E., Norton R.S., Nicholson S.E.;
RT "The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for
RT proteasomal degradation.";
RL J. Cell Biol. 190:129-141(2010).
RN [6]
RP INTERACTION WITH PAWR.
RX PubMed=20561531; DOI=10.1016/j.jmb.2010.06.017;
RA Filippakopoulos P., Low A., Sharpe T.D., Uppenberg J., Yao S., Kuang Z.,
RA Savitsky P., Lewis R.S., Nicholson S.E., Norton R.S., Bullock A.N.;
RT "Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-
RT containing proteins SPSB1, SPSB2, and SPSB4.";
RL J. Mol. Biol. 401:389-402(2010).
CC -!- FUNCTION: Substrate recognition component of a SCF-like ECS (Elongin
CC BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which
CC mediates the ubiquitination and subsequent proteasomal degradation of
CC target proteins (By similarity). Negatively regulates nitric oxide (NO)
CC production and limits cellular toxicity in activated macrophages by
CC mediating the ubiquitination and proteasomal degradation of NOS2 (By
CC similarity). Acts as a bridge which links NOS2 with the ECS E3
CC ubiquitin ligase complex components ELOC and CUL5 (By similarity).
CC Diminishes EphB2-dependent cell repulsive responses by mediating the
CC ubiquitination and degradation of the EphB2/CTF2 (By similarity).
CC Regulates cellular clock function by mediating ubiquitination and
CC proteasomal degradation of the circadian transcriptional repressor
CC NR1D1 (By similarity). {ECO:0000250|UniProtKB:Q96A44}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the probable ECS(SPSB4) E3 ubiquitin-protein
CC ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and
CC SPSB4 (By similarity). Interacts with CUL5; RNF7; ELOB and ELOC (By
CC similarity). Interacts with MET (PubMed:16369487). Interacts (via
CC B30.2/SPRY domain) with PAWR; this interaction occurs in association
CC with the Elongin BC complex (PubMed:16369487, PubMed:20561531).
CC Interacts with NOS2 (PubMed:20603330). Interacts with EPHB2 (By
CC similarity). {ECO:0000250|UniProtKB:Q96A44,
CC ECO:0000269|PubMed:16369487, ECO:0000269|PubMed:20561531,
CC ECO:0000269|PubMed:20603330}.
CC -!- INTERACTION:
CC Q8R5B6; Q96IZ0: PAWR; Xeno; NbExp=3; IntAct=EBI-8821982, EBI-595869;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q96A44}. Note=Exhibits a diffuse cytosolic
CC localization. {ECO:0000250|UniProtKB:Q96A44}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8R5B6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R5B6-2; Sequence=VSP_018614;
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin ligase
CC complexes (By similarity). Essential for its ability to link NOS2 and
CC the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q96A44}.
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; AF403039; AAL57358.2; -; mRNA.
DR EMBL; AK083698; BAC38995.1; -; mRNA.
DR EMBL; AK142195; BAE24972.1; -; mRNA.
DR EMBL; BC023083; AAH23083.1; -; mRNA.
DR EMBL; BC055705; AAH55705.1; -; mRNA.
DR EMBL; BC094332; AAH94332.1; -; mRNA.
DR CCDS; CCDS23419.1; -. [Q8R5B6-1]
DR RefSeq; NP_660116.1; NM_145134.3. [Q8R5B6-1]
DR AlphaFoldDB; Q8R5B6; -.
DR SMR; Q8R5B6; -.
DR BioGRID; 229277; 1.
DR DIP; DIP-29002N; -.
DR IntAct; Q8R5B6; 1.
DR STRING; 10090.ENSMUSP00000057849; -.
DR PhosphoSitePlus; Q8R5B6; -.
DR PaxDb; Q8R5B6; -.
DR PRIDE; Q8R5B6; -.
DR ProteomicsDB; 254540; -. [Q8R5B6-1]
DR ProteomicsDB; 254541; -. [Q8R5B6-2]
DR Antibodypedia; 77081; 12 antibodies from 8 providers.
DR Ensembl; ENSMUST00000055433; ENSMUSP00000057849; ENSMUSG00000046997. [Q8R5B6-1]
DR GeneID; 211949; -.
DR KEGG; mmu:211949; -.
DR UCSC; uc009rcx.1; mouse. [Q8R5B6-1]
DR UCSC; uc009rcy.1; mouse. [Q8R5B6-2]
DR CTD; 92369; -.
DR MGI; MGI:2183445; Spsb4.
DR VEuPathDB; HostDB:ENSMUSG00000046997; -.
DR eggNOG; KOG3953; Eukaryota.
DR GeneTree; ENSGT01030000234629; -.
DR HOGENOM; CLU_046756_0_1_1; -.
DR InParanoid; Q8R5B6; -.
DR OMA; SWNADDR; -.
DR OrthoDB; 938259at2759; -.
DR PhylomeDB; Q8R5B6; -.
DR TreeFam; TF312822; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 211949; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Spsb4; mouse.
DR PRO; PR:Q8R5B6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8R5B6; protein.
DR Bgee; ENSMUSG00000046997; Expressed in floor plate of midbrain and 208 other tissues.
DR Genevisible; Q8R5B6; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:1902916; P:positive regulation of protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISO:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 2.60.120.920; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
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 Alternative splicing; Biological rhythms; Cytoplasm; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..273
FT /note="SPRY domain-containing SOCS box protein 4"
FT /id="PRO_0000238478"
FT DOMAIN 34..233
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT DOMAIN 234..273
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT VAR_SEQ 232..273
FT /note="PEPLPLMDLCRRSIRSALGRQRLRDIGSLPLPQSLKNYLQYQ -> RKCPSL
FT GGQGCQDVLPGESWGEGERSK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018614"
SQ SEQUENCE 273 AA; 30286 MW; 623749B6F8C31B22 CRC64;
MGQKLSGSLK SVEVREPALR PAKRELRGLE PGRPARLDQL LDMPAAGLAV QLRHAWNPED
RSLNVFVKDD DRLTFHRHPV AQSTDGIRGK VGHARGLHAW QIHWPARQRG THAVVGVATA
RAPLHSVGYT ALVGSDSESW GWDLGRSRLY HDGKNRPGVA YPAFLGPDEA FALPDSLLVV
LDMDEGTLSF IVDGQYLGVA FRGLKGKKLY PVVSAVWGHC EVTMRYINGL DPEPLPLMDL
CRRSIRSALG RQRLRDIGSL PLPQSLKNYL QYQ
