ID SH3R1_RAT Reviewed; 894 AA.
AC Q71F54;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 134.
DE RecName: Full=E3 ubiquitin-protein ligase SH3RF1;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q7Z6J0};
DE AltName: Full=Plenty of SH3s;
DE Short=Protein POSH;
DE AltName: Full=RING-type E3 ubiquitin transferase SH3RF1 {ECO:0000305};
DE AltName: Full=SH3 domain-containing RING finger protein 1;
DE AltName: Full=SH3 multiple domains protein 2;
GN Name=Sh3rf1; Synonyms=Posh, Posh1 {ECO:0000250|UniProtKB:Q7Z6J0}, Sh3md2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MAP3K10; MAP3K11; DLK1;
RP MAP2K4; MAP2K7; MAPK8 AND MAPK9, UBIQUITINATION, AND FUNCTION.
RC STRAIN=New England Deaconess Hospital;
RX PubMed=12514131; DOI=10.1093/emboj/cdg021;
RA Xu Z., Kukekov N.V., Greene L.A.;
RT "POSH acts as a scaffold for a multiprotein complex that mediates JNK
RT activation in apoptosis.";
RL EMBO J. 22:252-261(2003).
RN [2]
RP INTERACTION WITH SIAH1.
RX PubMed=16230351; DOI=10.1074/jbc.m509060200;
RA Xu Z., Sproul A., Wang W., Kukekov N., Greene L.A.;
RT "Siah1 interacts with the scaffold protein POSH to promote JNK activation
RT and apoptosis.";
RL J. Biol. Chem. 281:303-312(2006).
RN [3]
RP INTERACTION WITH MAPK8IP, AND SUBCELLULAR LOCATION.
RX PubMed=16571722; DOI=10.1074/jbc.m601056200;
RA Kukekov N.V., Xu Z., Greene L.A.;
RT "Direct interaction of the molecular scaffolds POSH and JIP is required for
RT apoptotic activation of JNKs.";
RL J. Biol. Chem. 281:15517-15524(2006).
RN [4]
RP INTERACTION WITH SH3RF2, UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
RX PubMed=22128169; DOI=10.1074/jbc.m111.269431;
RA Wilhelm M., Kukekov N.V., Schmit T.L., Biagas K.V., Sproul A.A., Gire S.,
RA Maes M.E., Xu Z., Greene L.A.;
RT "Sh3rf2/POSHER protein promotes cell survival by RING-mediated proteasomal
RT degradation of the c-Jun N-terminal kinase scaffold POSH (Plenty of SH3s)
RT protein.";
RL J. Biol. Chem. 287:2247-2256(2012).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Has E3 ubiquitin-protein ligase activity. In the absence of
CC an external substrate, it can catalyze self-ubiquitination. Stimulates
CC ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-
CC dependent and clathrin-independent endocytosis (By similarity). Acts as
CC a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing
CC different components of the JNK pathway, including RAC1 or RAC2,
CC MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2
CC into a functional multiprotein complex to ensure the effective
CC activation of the JNK signaling pathway (PubMed:12514131). Regulates
CC the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper
CC 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1
CC and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in
CC CD8(+) T-cells. Plays a crucial role in the migration of neocortical
CC neurons in the developing brain. Controls proper cortical neuronal
CC migration and the formation of proximal cytoplasmic dilation in the
CC leading process (PCDLP) in migratory neocortical neurons by regulating
CC the proper localization of activated RAC1 and F-actin assembly (By
CC similarity). {ECO:0000250|UniProtKB:Q69ZI1,
CC ECO:0000250|UniProtKB:Q7Z6J0, ECO:0000269|PubMed:12514131}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q7Z6J0};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with HERP1. Interacts with RAC1; in a GTP-dependent
CC manner (By similarity). Interacts with MAP3K10/MLK2 and MAP3K11/MLK3.
CC Interacts with MAPK8IP; this interaction leads to the PJAC complex
CC (POSH-JIP or SH3RF1/MAPK8IP apoptotic complex) with a 1:1 ratio.
CC Interacts with SIAH1. Probably part of a signaling complex that may
CC contain SH3RF1, MAPK8IP, DLK1, MAP2K4/MKK4, MAP2K7/MKK7, MAPK8/JNK1,
CC MAPK9/JNK2, AKT1 and AKT2 (PubMed:12514131, PubMed:16230351,
CC PubMed:16571722). Found in a complex with RAC2, MAP3K7/TAK1,
CC MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2. Found in a
CC complex with RAC1, MAP3K11/MLK3, MAP2K7/MKK7, MAPK8IP1/JIP1 and
CC MAPK8/JNK1 (By similarity). Interacts with SH3RF2 (PubMed:22128169).
CC {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000250|UniProtKB:Q7Z6J0,
CC ECO:0000269|PubMed:12514131, ECO:0000269|PubMed:16230351,
CC ECO:0000269|PubMed:16571722, ECO:0000269|PubMed:22128169}.
CC -!- INTERACTION:
CC Q71F54; Q920M9: Siah1; NbExp=2; IntAct=EBI-957526, EBI-957514;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:16571722}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q69ZI1}. Golgi apparatus, trans-Golgi network
CC {ECO:0000250|UniProtKB:Q69ZI1}. Note=Colocalizes, with AKT2, in
CC lamellipodia. Colocalizes, with HERP1, in trans-Golgi network.
CC {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000250|UniProtKB:Q7Z6J0}.
CC -!- DOMAIN: The RING finger domain is required for ubiquitin ligase
CC activity and autoubiquitination. {ECO:0000250|UniProtKB:Q7Z6J0}.
CC -!- PTM: Phosphorylated at Ser-305 by AKT1 and AKT2. When phosphorylated,
CC it has reduced ability to bind Rac. {ECO:0000250|UniProtKB:Q7Z6J0}.
CC -!- PTM: Autoubiquitinated. Ubiquitinated by SH3RF2, leading to proteasome-
CC mediated degradation. {ECO:0000269|PubMed:12514131,
CC ECO:0000269|PubMed:22128169}.
CC -!- SIMILARITY: Belongs to the SH3RF family. {ECO:0000305}.
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DR EMBL; AF515735; AAQ08184.1; -; mRNA.
DR RefSeq; NP_942059.1; NM_198764.1.
DR RefSeq; XP_017455595.1; XM_017600106.1.
DR AlphaFoldDB; Q71F54; -.
DR SMR; Q71F54; -.
DR IntAct; Q71F54; 1.
DR STRING; 10116.ENSRNOP00000013815; -.
DR iPTMnet; Q71F54; -.
DR PhosphoSitePlus; Q71F54; -.
DR PaxDb; 10116-ENSRNOP00000013815; -.
DR Ensembl; ENSRNOT00000013816.4; ENSRNOP00000013815.1; ENSRNOG00000010358.8.
DR Ensembl; ENSRNOT00055022560; ENSRNOP00055018322; ENSRNOG00055013164.
DR Ensembl; ENSRNOT00060025837; ENSRNOP00060020657; ENSRNOG00060015072.
DR Ensembl; ENSRNOT00065006036; ENSRNOP00065004315; ENSRNOG00065004143.
DR GeneID; 306417; -.
DR KEGG; rno:306417; -.
DR UCSC; RGD:735154; rat.
DR AGR; RGD:735154; -.
DR CTD; 57630; -.
DR RGD; 735154; Sh3rf1.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000155875; -.
DR HOGENOM; CLU_015769_1_0_1; -.
DR InParanoid; Q71F54; -.
DR OMA; NMIIAPS; -.
DR OrthoDB; 5407056at2759; -.
DR PhylomeDB; Q71F54; -.
DR TreeFam; TF105571; -.
DR Reactome; R-RNO-9013424; RHOV GTPase cycle.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q71F54; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000010358; Expressed in duodenum and 18 other cell types or tissues.
DR Genevisible; Q71F54; RN.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0043370; P:regulation of CD4-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:2000564; P:regulation of CD8-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
DR GO; GO:1904044; P:response to aldosterone; IEP:RGD.
DR CDD; cd16748; RING-HC_SH3RF1; 1.
DR CDD; cd11930; SH3_SH3RF1_2; 1.
DR CDD; cd11785; SH3_SH3RF_C; 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 4.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR035816; SH3RF1/SH3RF3_SH3_4.
DR InterPro; IPR035795; SH3RF1_SH3_2.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR14167:SF62; E3 UBIQUITIN-PROTEIN LIGASE SH3RF3; 1.
DR PANTHER; PTHR14167; SH3 DOMAIN-CONTAINING; 1.
DR Pfam; PF00018; SH3_1; 2.
DR Pfam; PF14604; SH3_9; 2.
DR Pfam; PF13923; zf-C3HC4_2; 1.
DR PRINTS; PR00499; P67PHOX.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00184; RING; 1.
DR SMART; SM00326; SH3; 4.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR SUPFAM; SSF50044; SH3-domain; 4.
DR PROSITE; PS50002; SH3; 4.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Golgi apparatus; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..894
FT /note="E3 ubiquitin-protein ligase SH3RF1"
FT /id="PRO_0000334154"
FT DOMAIN 134..193
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 196..259
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 453..514
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 835..894
FT /note="SH3 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT ZN_FING 12..53
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 274..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..363
FT /note="Interaction with RAC1"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6J0"
FT REGION 448..551
FT /note="Interaction with AKT2"
FT /evidence="ECO:0000250"
FT REGION 526..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..751
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 693..710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6J0"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6J0"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 894 AA; 93879 MW; E7CB1B7E6330C62D CRC64;
MDESALLDLL ECPVCLERLD ASAKVLPCQH TFCKRCLLGI VGSRNELRCP ECRTLVGSGV
DELPSNILLV RLLDGIKQRP WKPGPGGGGS TTCTNVLRAQ GSTVVNCGSK DLQSPQCGQQ
PRVQAWSPPV RGIPQLPCAK ALYNYEGKEP GDLKFSKGDI IILRRQVDEN WYHGEVNGVH
GFFPTNFVQI IKPLPQPPPQ CKALYDFEVK DKEADKDCLP FAKDDVLTVI RRVDENWAEG
MLADKIGIFP ISYVEFNSAA KQLIEWDKPP VPGVDTAECP SATAAQSSSA SKHSDTKKNT
RKRHSFTSLT MANKSSQASQ NRHSMEISPP VLISSSNPTA AARISELSGL SCSAPSQVHI
STTGLIVTPP PSSPVTTGPS FTFPTDVPYQ AALGTMNPPL PPPPLLATTV LASTPSGATA
AAVAAAAAAV AAGVGPRPAV GSTEQIAHLR PQTRPSVYVA IYPYTPRKED ELELRKGEMF
LVFERCQDGW YKGTSMHTSK IGVFPGNYVA PVTRAVTNAS QAKVPMSTAG QASRGVTMVS
PSTAGGPAQK PQGNGVAGNP SVVPTAVVSA AHIQTSPQAK VLLHMTGQMT VNQARNAVRT
VAAHNQERPT AAVTPIQVQN AACIGPASVG LPHHSLASQP LPPMVGPAAH IAAVNINRTS
VPLACAAGAS SLASPNMTTA ALETEPSGRT VTILPGLPTS PESAASACGN SSAVKPDKDS
KKEKKGLLKL LSGASTKRKP RVSPPASPTL DVELGSGEVP LQGAVGPELP LGGVHGRVGS
CPTDGDGPVA AGTAALAQDA FHRKTSSLDS AVPIAPPPRQ ACSSLGPVMN EARPVVCERH
RVVVSYPPQS EAELELKEGD IVFVHKKRED GWFKGTLQRN GKTGLFPGSF VENI
//
