SPSB2_MOUSE
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 03-AUG-2022, entry version 156.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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., Lu J.,
RA Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.;
RT "Comparative sequence analysis of a gene-rich cluster at human chromosome
RT 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., 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 [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 project:
RT 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., 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, 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., 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).
RN [7]
RP STRUCTURE BY NMR OF 12-224, INTERACTION WITH PAWR AND MET, AND MUTAGENESIS
RP OF TYR-120; 123-LEU--GLY-125; 141-TYR--GLN-143; 151-GLN-TYR-152;
RP 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., 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).
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 (PubMed:20603330). Negatively regulates nitric oxide
CC (NO) production and limits cellular toxicity in activated macrophages
CC by mediating the ubiquitination and proteasomal degradation of NOS2
CC (PubMed:20603330). Acts as a bridge which links NOS2 with the ECS E3
CC ubiquitin ligase complex components ELOC and CUL5 (By similarity).
CC {ECO:0000250|UniProtKB:Q99619, 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 and
CC SPSB2 (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. {ECO:0000250|UniProtKB:Q99619,
CC ECO:0000269|PubMed:16369487, ECO:0000269|PubMed:20561531,
CC ECO:0000269|PubMed:20603330}.
CC -!- INTERACTION:
CC O88838; 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 -!- 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:Q99619}.
CC -!- SIMILARITY: Belongs to the SPSB family. {ECO:0000305}.
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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 AlphaFoldDB; O88838; -.
DR BMRB; O88838; -.
DR SMR; O88838; -.
DR BioGRID; 200055; 1.
DR DIP; DIP-29001N; -.
DR IntAct; O88838; 2.
DR STRING; 10090.ENSMUSP00000060124; -.
DR BindingDB; O88838; -.
DR ChEMBL; CHEMBL3325309; -.
DR PhosphoSitePlus; O88838; -.
DR MaxQB; O88838; -.
DR PaxDb; O88838; -.
DR PRIDE; O88838; -.
DR ProteomicsDB; 261634; -. [O88838-1]
DR ProteomicsDB; 261635; -. [O88838-2]
DR Antibodypedia; 11257; 92 antibodies from 21 providers.
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 VEuPathDB; HostDB:ENSMUSG00000038451; -.
DR eggNOG; KOG3953; Eukaryota.
DR GeneTree; ENSGT01030000234629; -.
DR InParanoid; O88838; -.
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 BioGRID-ORCS; 14794; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Nabp1; mouse.
DR EvolutionaryTrace; O88838; -.
DR PRO; PR:O88838; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; O88838; protein.
DR Bgee; ENSMUSG00000038451; Expressed in granulocyte and 156 other tissues.
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:ubiquitin ligase-substrate adaptor activity; 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 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 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; Cytoplasm; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..264
FT /note="SPRY domain-containing SOCS box protein 2"
FT /id="PRO_0000238475"
FT DOMAIN 26..221
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT DOMAIN 222..264
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 222..264
FT /note="VEEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK -> GEIRT
FT RCGEITTLGNGLGWKLMVGAQEVGFLSLWPVT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_018613"
FT MUTAGEN 100..101
FT /note="RG->AA: Loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 102..103
FT /note="TH->AA: Significant loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 118..119
FT /note="DH->AA: No loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 120
FT /note="Y->A: Loss of interaction with PARW. No effect on
FT interaction with MET. Loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:16369487,
FT ECO:0000269|PubMed:20561531, ECO:0000269|PubMed:20603330"
FT MUTAGEN 120
FT /note="Y->F: Loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 123..125
FT /note="LLG->AAA: Loss of interaction with MET and PARW.
FT Loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:16369487,
FT ECO:0000269|PubMed:20561531, ECO:0000269|PubMed:20603330"
FT MUTAGEN 126..128
FT /note="SNS->AAA: Loss of interaction with PAWR. Significant
FT loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:20561531,
FT ECO:0000269|PubMed:20603330"
FT MUTAGEN 141..143
FT /note="YHQ->AAA: Strongly reduced interaction with MET and
FT PARW."
FT /evidence="ECO:0000269|PubMed:16369487"
FT MUTAGEN 151..152
FT /note="QY->AA: Loss of interaction with MET and PARW."
FT /evidence="ECO:0000269|PubMed:16369487"
FT MUTAGEN 160..161
FT /note="QL->AA: No loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 188..189
FT /note="GP->AA: Strongly reduced interaction with MET. Loss
FT of interaction with PARW."
FT /evidence="ECO:0000269|PubMed:16369487"
FT MUTAGEN 198
FT /note="T->A: No loss of interaction with PAWR."
FT /evidence="ECO:0000269|PubMed:20561531"
FT MUTAGEN 206
FT /note="V->A: Loss of interaction with PARW. No effect on
FT interaction with MET. Loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:16369487,
FT ECO:0000269|PubMed:20561531, ECO:0000269|PubMed:20603330"
FT MUTAGEN 207
FT /note="W->A: Significant loss of interaction with NOS2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT HELIX 29..34
FT /evidence="ECO:0007829|PDB:3EK9"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:3EK9"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:3EK9"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:2AFJ"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 84..94
FT /evidence="ECO:0007829|PDB:3EK9"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:3EK9"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:2AFJ"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:2AFJ"
FT STRAND 165..172
FT /evidence="ECO:0007829|PDB:3EK9"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 185..191
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:3EK9"
FT STRAND 212..218
FT /evidence="ECO:0007829|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
