ID SPSB2_MOUSE Reviewed; 264 AA. AC O88838; Q8CBA5; Q91Z15; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 16-OCT-2019, entry version 143. DE RecName: Full=SPRY domain-containing SOCS box protein 2; DE Short=SSB-2; DE AltName: Full=Gene-rich cluster protein C9; GN Name=Spsb2; Synonyms=Grcc9, Ssb2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9445485; RA Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., RA Lu J., Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., RA Gibbs R.A.; RT "Comparative sequence analysis of a gene-rich cluster at human RT chromosome 12p13 and its syntenic region in mouse chromosome 6."; RL Genome Res. 8:29-40(1998). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Bone; 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=FVB/N; TISSUE=Mammary gland, 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, INTERACTION WITH NOS2, AND MUTAGENESIS OF 100-ARG-GLY-101; RP 102-THR-HIS-103; 118-ASP-HIS-119; TYR-120; 123-LEU--GLY-125; RP 126-SER--SER-128; 160-GLN-LEU-161; VAL-206 AND TRP-207. 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., RA Yao S., 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, AND MUTAGENESIS OF TYR-120; 123-LEU--GLY-125; RP 126-SER--SER-128; THR-198 AND VAL-206. RX PubMed=20561531; DOI=10.1016/j.jmb.2010.06.017; RA Filippakopoulos P., Low A., Sharpe T.D., Uppenberg J., Yao S., RA Kuang Z., Savitsky P., Lewis R.S., Nicholson S.E., Norton R.S., RA Bullock A.N.; RT "Structural basis for Par-4 recognition by the SPRY domain- and SOCS RT box-containing proteins SPSB1, SPSB2, and SPSB4."; RL J. Mol. Biol. 401:389-402(2010). RN [7] RP STRUCTURE BY NMR OF 12-224, INTERACTION WITH PAWR AND MET, AND RP MUTAGENESIS OF TYR-120; 123-LEU--GLY-125; 141-TYR--GLN-143; RP 151-GLN-TYR-152; 188-GLY-PRO-189 AND VAL-206. RX PubMed=16369487; DOI=10.1038/nsmb1034; RA Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., RA Smith B.J., 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 RT Par-4-binding residues."; RL Nat. Struct. Mol. Biol. 13:77-84(2006). CC -!- FUNCTION: Substrate recognition component of a SCF-like ECS CC (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase CC complex which mediates the ubiquitination and subsequent CC proteasomal degradation of target proteins (PubMed:20603330). CC Negatively regulates nitric oxide (NO) production and limits CC cellular toxicity in activated macrophages by mediating the CC ubiquitination and proteasomal degradation of NOS2 CC (PubMed:20603330). Acts as a bridge which links NOS2 with the ECS CC E3 ubiquitin ligase complex components ELOC and CUL5 (By CC similarity). {ECO:0000250|UniProtKB:Q99619, CC ECO:0000269|PubMed:20603330}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Component of the probable ECS(SPSB2) E3 ubiquitin-protein CC ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex CC and SPSB2 (By similarity). Interacts with CUL5, RNF7, ELOB and CC ELOC (By similarity). Interacts with MET (PubMed:16369487). CC Interacts (via B30.2/SPRY domain) with PAWR; this interaction CC occurs in association with the Elongin BC complex CC (PubMed:16369487, PubMed:20561531). Interacts with NOS2. CC {ECO:0000250|UniProtKB:Q99619, ECO:0000269|PubMed:16369487, CC ECO:0000269|PubMed:20561531, ECO:0000269|PubMed:20603330}. CC -!- INTERACTION: CC Q96IZ0:PAWR (xeno); NbExp=6; IntAct=EBI-8820410, EBI-595869; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q99619}. Note=Exhibits a diffuse cytosolic CC localization. {ECO:0000250|UniProtKB:Q99619}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O88838-1; Sequence=Displayed; CC Name=2; CC IsoId=O88838-2; Sequence=VSP_018613; CC Note=No experimental confirmation available.; 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 (By similarity). Essential for its ability to CC link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC CC and CUL5 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:Q99619}. 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; AC002397; AAC36017.1; -; Genomic_DNA. DR EMBL; AF403037; AAL57356.1; -; mRNA. DR EMBL; AK036451; BAC29435.1; -; mRNA. DR EMBL; AK148177; BAE28397.1; -; mRNA. DR EMBL; BC002005; AAH02005.1; -; mRNA. DR EMBL; BC010305; AAH10305.1; -; mRNA. DR CCDS; CCDS20529.1; -. [O88838-1] DR RefSeq; NP_001292979.1; NM_001306050.1. [O88838-1] DR RefSeq; NP_001292980.1; NM_001306051.1. [O88838-1] DR RefSeq; NP_001292981.1; NM_001306052.1. [O88838-1] DR RefSeq; NP_001292982.1; NM_001306053.1. DR RefSeq; NP_038567.1; NM_013539.2. [O88838-1] DR RefSeq; XP_006505630.1; XM_006505567.3. [O88838-1] DR PDB; 2AFJ; NMR; -; A=12-224. DR PDB; 3EK9; X-ray; 2.60 A; A=12-224. DR PDBsum; 2AFJ; -. DR PDBsum; 3EK9; -. DR SMR; O88838; -. DR BioGrid; 200055; 1. DR DIP; DIP-29001N; -. DR IntAct; O88838; 2. DR STRING; 10090.ENSMUSP00000060124; -. DR ChEMBL; CHEMBL3325309; -. DR PhosphoSitePlus; O88838; -. DR MaxQB; O88838; -. DR PaxDb; O88838; -. DR PRIDE; O88838; -. DR DNASU; 14794; -. DR Ensembl; ENSMUST00000047760; ENSMUSP00000041585; ENSMUSG00000038451. [O88838-1] DR Ensembl; ENSMUST00000052727; ENSMUSP00000060124; ENSMUSG00000038451. [O88838-1] DR Ensembl; ENSMUST00000112473; ENSMUSP00000108092; ENSMUSG00000038451. [O88838-2] DR GeneID; 14794; -. DR KEGG; mmu:14794; -. DR UCSC; uc009drw.1; mouse. [O88838-1] DR CTD; 84727; -. DR MGI; MGI:1315199; Spsb2. DR eggNOG; KOG3953; Eukaryota. DR eggNOG; ENOG410XQC1; LUCA. DR GeneTree; ENSGT00950000182795; -. DR HOGENOM; HOG000230524; -. DR InParanoid; O88838; -. DR KO; K10344; -. DR OMA; HAWEIGW; -. DR OrthoDB; 938259at2759; -. DR PhylomeDB; O88838; -. DR TreeFam; TF312822; -. DR Reactome; R-MMU-8951664; Neddylation. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR ChiTaRS; Nabp1; mouse. DR EvolutionaryTrace; O88838; -. DR PRO; PR:O88838; -. DR Proteomes; UP000000589; Chromosome 6. DR Bgee; ENSMUSG00000038451; Expressed in 188 organ(s), highest expression level in submandibular gland. DR ExpressionAtlas; O88838; baseline and differential. DR Genevisible; O88838; 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:protein binding, bridging involved in substrate recognition for ubiquitination; ISO:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR CDD; cd03719; SOCS_SSB2; 1. DR InterPro; IPR001870; B30.2/SPRY. 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 InterPro; IPR037340; SSB2_SOCS. DR Pfam; PF07525; SOCS_box; 1. DR Pfam; PF00622; SPRY; 1. DR SMART; SM00253; SOCS; 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; Alternative splicing; Complete proteome; Cytoplasm; KW Reference proteome; Ubl conjugation pathway. FT CHAIN 1 264 SPRY domain-containing SOCS box protein FT 2. FT /FTId=PRO_0000238475. FT DOMAIN 26 221 B30.2/SPRY. {ECO:0000255|PROSITE- FT ProRule:PRU00548}. FT DOMAIN 222 264 SOCS box. {ECO:0000255|PROSITE- FT ProRule:PRU00194}. FT VAR_SEQ 222 264 VEEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLL FT YK -> GEIRTRCGEITTLGNGLGWKLMVGAQEVGFLSLWP FT VT (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_018613. FT MUTAGEN 100 101 RG->AA: Loss of interaction with NOS2. FT {ECO:0000269|PubMed:20603330}. FT MUTAGEN 102 103 TH->AA: Significant loss of interaction FT with NOS2. {ECO:0000269|PubMed:20603330}. FT MUTAGEN 118 119 DH->AA: No loss of interaction with NOS2. FT {ECO:0000269|PubMed:20603330}. FT MUTAGEN 120 120 Y->A: Loss of interaction with PARW. No FT effect on interaction with MET. Loss of FT interaction with NOS2. FT {ECO:0000269|PubMed:16369487, FT ECO:0000269|PubMed:20561531, FT ECO:0000269|PubMed:20603330}. FT MUTAGEN 120 120 Y->F: Loss of interaction with NOS2. FT {ECO:0000269|PubMed:20603330}. FT MUTAGEN 123 125 LLG->AAA: Loss of interaction with MET FT and PARW. Loss of interaction with NOS2. FT {ECO:0000269|PubMed:16369487, FT ECO:0000269|PubMed:20561531, FT ECO:0000269|PubMed:20603330}. FT MUTAGEN 126 128 SNS->AAA: Loss of interaction with PAWR. FT Significant loss of interaction with FT NOS2. {ECO:0000269|PubMed:20561531, FT ECO:0000269|PubMed:20603330}. FT MUTAGEN 141 143 YHQ->AAA: Strongly reduced interaction FT with MET and PARW. FT {ECO:0000269|PubMed:16369487}. FT MUTAGEN 151 152 QY->AA: Loss of interaction with MET and FT PARW. {ECO:0000269|PubMed:16369487}. FT MUTAGEN 160 161 QL->AA: No loss of interaction with NOS2. FT {ECO:0000269|PubMed:20603330}. FT MUTAGEN 188 189 GP->AA: Strongly reduced interaction with FT MET. Loss of interaction with PARW. FT {ECO:0000269|PubMed:16369487}. FT MUTAGEN 198 198 T->A: No loss of interaction with PAWR. FT {ECO:0000269|PubMed:20561531}. FT MUTAGEN 206 206 V->A: Loss of interaction with PARW. No FT effect on interaction with MET. Loss of FT interaction with NOS2. FT {ECO:0000269|PubMed:16369487, FT ECO:0000269|PubMed:20561531, FT ECO:0000269|PubMed:20603330}. FT MUTAGEN 207 207 W->A: Significant loss of interaction FT with NOS2. {ECO:0000269|PubMed:20603330}. FT HELIX 29 34 {ECO:0000244|PDB:3EK9}. FT HELIX 40 45 {ECO:0000244|PDB:3EK9}. FT STRAND 47 53 {ECO:0000244|PDB:3EK9}. FT STRAND 57 60 {ECO:0000244|PDB:3EK9}. FT HELIX 61 63 {ECO:0000244|PDB:3EK9}. FT STRAND 65 68 {ECO:0000244|PDB:3EK9}. FT TURN 72 74 {ECO:0000244|PDB:2AFJ}. FT STRAND 75 81 {ECO:0000244|PDB:3EK9}. FT STRAND 84 94 {ECO:0000244|PDB:3EK9}. FT HELIX 97 99 {ECO:0000244|PDB:3EK9}. FT STRAND 105 109 {ECO:0000244|PDB:3EK9}. FT STRAND 116 119 {ECO:0000244|PDB:3EK9}. FT STRAND 130 134 {ECO:0000244|PDB:3EK9}. FT TURN 135 137 {ECO:0000244|PDB:3EK9}. FT STRAND 139 143 {ECO:0000244|PDB:3EK9}. FT STRAND 150 153 {ECO:0000244|PDB:2AFJ}. FT HELIX 157 160 {ECO:0000244|PDB:2AFJ}. FT STRAND 165 172 {ECO:0000244|PDB:3EK9}. FT TURN 173 176 {ECO:0000244|PDB:3EK9}. FT STRAND 177 182 {ECO:0000244|PDB:3EK9}. FT STRAND 185 191 {ECO:0000244|PDB:3EK9}. FT STRAND 199 205 {ECO:0000244|PDB:3EK9}. FT STRAND 212 218 {ECO:0000244|PDB:3EK9}. SQ SEQUENCE 264 AA; 28938 MW; E71985597D9B38CB CRC64; MGQTALARGS SSTPTSQALY SDFSPPEGLE ELLSAPPPDL VAQRHHGWNP KDCSENIDVK EGGLCFERRP VAQSTDGVRG KRGYSRGLHA WEISWPLEQR GTHAVVGVAT ALAPLQADHY AALLGSNSES WGWDIGRGKL YHQSKGLEAP QYPAGPQGEQ LVVPERLLVV LDMEEGTLGY SIGGTYLGPA FRGLKGRTLY PSVSAVWGQC QVRIRYMGER RVEEPQSLLH LSRLCVRHAL GDTRLGQIST LPLPPAMKRY LLYK //