SPSB1_MOUSE
ID SPSB1_MOUSE Reviewed; 273 AA.
AC Q9D5L7; Q5FWI0; Q8BJA4;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=SPRY domain-containing SOCS box protein 1;
DE Short=SSB-1;
GN Name=Spsb1; Synonyms=Ssb1;
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 (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Aorta, Embryo, Pituitary anterior lobe, Spleen, Testis, and Vein;
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 ELONGIN BC COMPLEX.
RX PubMed=16498413; DOI=10.1038/sj.emboj.7600994;
RA Woo J.S., Imm J.H., Min C.K., Kim K.J., Cha S.S., Oh B.H.;
RT "Structural and functional insights into the B30.2/SPRY domain.";
RL EMBO J. 25:1353-1363(2006).
RN [6]
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 [7]
RP INTERACTION WITH PAWR, AND DOMAIN.
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 the NOS2 with the ECS E3
CC ubiquitin ligase complex components ELOC and CUL5 (By similarity).
CC {ECO:0000250|UniProtKB:Q96BD6}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the probable ECS(SPSB1) E3 ubiquitin-protein
CC ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and
CC SPSB1 (By similarity). Interacts with CUL5, RNF7, ELOB and ELOC (By
CC similarity). Directly interacts with MET tyrosine kinase domain in the
CC presence and in the absence of HGF, however HGF treatment has a
CC positive effect on this interaction (PubMed:16369487). When
CC phosphorylated, interacts with RASA1 without affecting its stability
CC (By similarity). Interacts (via B30.2/SPRY domain) with PAWR; this
CC interaction is direct and occurs in association with the Elongin BC
CC complex (PubMed:16369487, PubMed:16498413, PubMed:20561531).Interacts
CC with EPHB2 (By similarity). Interacts with NOS2 (PubMed:20603330).
CC {ECO:0000250|UniProtKB:Q96BD6, ECO:0000269|PubMed:16369487,
CC ECO:0000269|PubMed:16498413, ECO:0000269|PubMed:20561531,
CC ECO:0000269|PubMed:20603330}.
CC -!- INTERACTION:
CC Q9D5L7; Q96IZ0: PAWR; Xeno; NbExp=2; IntAct=EBI-8821912, EBI-595869;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q96BD6}. Note=Exhibits a diffuse cytosolic
CC localization. {ECO:0000250|UniProtKB:Q96BD6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9D5L7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9D5L7-2; Sequence=VSP_018612;
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:Q96BD6}.
CC -!- DOMAIN: The B30.2/SPRY domain is involved in MET and PAWR binding.
CC {ECO:0000269|PubMed:16369487, ECO:0000269|PubMed:20561531}.
CC -!- SIMILARITY: Belongs to the SPSB family. {ECO:0000305}.
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DR EMBL; AF403036; AAL57355.1; -; mRNA.
DR EMBL; AK015181; BAB29738.1; -; mRNA.
DR EMBL; AK003707; BAC25049.1; -; mRNA.
DR EMBL; AK030417; BAC26954.1; -; mRNA.
DR EMBL; AK040909; BAC30739.1; -; mRNA.
DR EMBL; AK089767; BAC40957.1; -; mRNA.
DR EMBL; AK160081; BAE35613.1; -; mRNA.
DR EMBL; AK172334; BAE42952.1; -; mRNA.
DR EMBL; BC046787; AAH46787.1; -; mRNA.
DR EMBL; BC057563; AAH57563.1; -; mRNA.
DR EMBL; BC089357; AAH89357.1; -; mRNA.
DR CCDS; CCDS18966.1; -. [Q9D5L7-1]
DR RefSeq; NP_083311.1; NM_029035.2. [Q9D5L7-1]
DR RefSeq; XP_006539297.1; XM_006539234.2. [Q9D5L7-1]
DR RefSeq; XP_011248646.1; XM_011250344.2. [Q9D5L7-1]
DR RefSeq; XP_011248647.1; XM_011250345.2. [Q9D5L7-1]
DR AlphaFoldDB; Q9D5L7; -.
DR SMR; Q9D5L7; -.
DR DIP; DIP-29000N; -.
DR IntAct; Q9D5L7; 1.
DR STRING; 10090.ENSMUSP00000048969; -.
DR iPTMnet; Q9D5L7; -.
DR PhosphoSitePlus; Q9D5L7; -.
DR PaxDb; Q9D5L7; -.
DR PRIDE; Q9D5L7; -.
DR ProteomicsDB; 254534; -. [Q9D5L7-1]
DR ProteomicsDB; 254535; -. [Q9D5L7-2]
DR Antibodypedia; 1144; 63 antibodies from 19 providers.
DR Ensembl; ENSMUST00000038562; ENSMUSP00000048969; ENSMUSG00000039911. [Q9D5L7-1]
DR Ensembl; ENSMUST00000105684; ENSMUSP00000101309; ENSMUSG00000039911. [Q9D5L7-1]
DR Ensembl; ENSMUST00000105685; ENSMUSP00000101310; ENSMUSG00000039911. [Q9D5L7-1]
DR GeneID; 74646; -.
DR KEGG; mmu:74646; -.
DR UCSC; uc008vxf.1; mouse. [Q9D5L7-1]
DR CTD; 80176; -.
DR MGI; MGI:1921896; Spsb1.
DR VEuPathDB; HostDB:ENSMUSG00000039911; -.
DR eggNOG; KOG3953; Eukaryota.
DR GeneTree; ENSGT01030000234629; -.
DR HOGENOM; CLU_046756_0_1_1; -.
DR InParanoid; Q9D5L7; -.
DR OMA; SESYGWD; -.
DR OrthoDB; 938259at2759; -.
DR PhylomeDB; Q9D5L7; -.
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; 74646; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Spsb1; mouse.
DR PRO; PR:Q9D5L7; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9D5L7; protein.
DR Bgee; ENSMUSG00000039911; Expressed in decidua and 216 other tissues.
DR ExpressionAtlas; Q9D5L7; baseline and differential.
DR Genevisible; Q9D5L7; 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:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
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; 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; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..273
FT /note="SPRY domain-containing SOCS box protein 1"
FT /id="PRO_0000238473"
FT DOMAIN 33..231
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT DOMAIN 232..273
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT MOD_RES 31
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q96BD6"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_018612"
FT CONFLICT 11
FT /note="T -> S (in Ref. 1; BAC40957)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="H -> R (in Ref. 1; BAC40957)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="R -> H (in Ref. 1; BAC40957)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 273 AA; 30785 MW; 2CBA3B50A3240177 CRC64;
MGQKVTGGIK TVDMRDPTYR PLKQELQGLD YCKPTRLDLL LDMPPVSYDV QLLHSWNNND
RSLNVFVKED DKLIFHRHPV AQSTDAIRGK VGYTRGLHVW QITWAMRQRG THAVVGVATA
DAPLHSVGYT TLVGNNHESW GWDLGRNRLY HDGKNQPSKT YPAFLEPDET FIVPDSFLVA
LDMDDGTLSF IVDGQYMGVA FRGLKGKKLY PVVSAVWGHC EIRMRYLNGL DPEPLPLMDL
CRRSVRLALG KERLGAIPAL PLPASLKAYL LYQ
