SH3R1_HUMAN
ID SH3R1_HUMAN Reviewed; 888 AA.
AC Q7Z6J0; Q05BT2; Q8IW46; Q9HAM2; Q9P234;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=E3 ubiquitin-protein ligase SH3RF1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:15659549, ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164};
DE AltName: Full=Plenty of SH3s;
DE Short=Protein POSH;
DE AltName: Full=RING finger protein 142;
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;
GN Synonyms=KIAA1494, POSH, POSH1 {ECO:0000303|PubMed:20696164}, RNF142,
GN SH3MD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 140-888 (ISOFORM 2).
RC TISSUE=Eye, and Ovary;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-712 (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 251-888 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [4]
RP INTERACTION WITH MAP3K10; MAP3K11; DLK1; MAP2K4; MAP2K7; MAPK8 AND MAPK9.
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 [5]
RP INTERACTION WITH AKT1 AND AKT2.
RX PubMed=14504284; DOI=10.1074/jbc.m307357200;
RA Figueroa C., Tarras S., Taylor J., Vojtek A.B.;
RT "Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling
RT complex.";
RL J. Biol. Chem. 278:47922-47927(2003).
RN [6]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, CATALYTIC ACTIVITY, FUNCTION
RP (MICROBIAL INFECTION), SUBCELLULAR LOCATION, AND SELF-UBIQUITINATION.
RX PubMed=15659549; DOI=10.1073/pnas.0408717102;
RA Alroy I., Tuvia S., Greener T., Gordon D., Barr H.M., Taglicht D.,
RA Mandil-Levin R., Ben-Avraham D., Konforty D., Nir A., Levius O.,
RA Bicoviski V., Dori M., Cohen S., Yaar L., Erez O., Propheta-Meiran O.,
RA Koskas M., Caspi-Bachar E., Alchanati I., Sela-Brown A., Moskowitz H.,
RA Tessmer U., Schubert U., Reiss Y.;
RT "The trans-Golgi network-associated human ubiquitin-protein ligase POSH is
RT essential for HIV type 1 production.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1478-1483(2005).
RN [7]
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 [8]
RP INTERACTION WITH MAPK8IP.
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 [9]
RP INTERACTION WITH AKT1 AND AKT2, PHOSPHORYLATION AT SER-304, MUTAGENESIS OF
RP SER-304, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17535800; DOI=10.1074/jbc.m704321200;
RA Lyons T.R., Thorburn J., Ryan P.W., Thorburn A., Anderson S.M.,
RA Kassenbrock C.K.;
RT "Regulation of the pro-apoptotic scaffolding protein POSH by Akt.";
RL J. Biol. Chem. 282:21987-21997(2007).
RN [10]
RP INTERACTION WITH HERP1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-14.
RX PubMed=17420289; DOI=10.1083/jcb.200611036;
RA Tuvia S., Taglicht D., Erez O., Alroy I., Alchanati I., Bicoviski V.,
RA Dori-Bachash M., Ben-Avraham D., Reiss Y.;
RT "The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial
RT control of Herp.";
RL J. Cell Biol. 177:51-61(2007).
RN [11]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND CATALYTIC ACTIVITY.
RX PubMed=19710010; DOI=10.1074/jbc.m109.041582;
RA Lin D.H., Yue P., Pan C.Y., Sun P., Zhang X., Han Z., Roos M., Caplan M.,
RA Giebisch G., Wang W.H.;
RT "POSH stimulates the ubiquitination and the clathrin-independent
RT endocytosis of ROMK1 channels.";
RL J. Biol. Chem. 284:29614-29624(2009).
RN [12]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, CATALYTIC ACTIVITY,
RP AUTOUBIQUITINATION, MUTAGENESIS OF CYS-28 AND HIS-30, AND INTERACTION WITH
RP RAC1.
RX PubMed=20696164; DOI=10.1016/j.febslet.2010.07.060;
RA Kaerkkaeinen S., van der Linden M., Renkema G.H.;
RT "POSH2 is a RING finger E3 ligase with Rac1 binding activity through a
RT partial CRIB domain.";
RL FEBS Lett. 584:3867-3872(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304 AND SER-532, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Has E3 ubiquitin-protein ligase activity. In the absence of
CC an external substrate, it can catalyze self-ubiquitination
CC (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of
CC potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-
CC independent endocytosis (PubMed:19710010). Acts as a scaffold protein
CC that coordinates with MAPK8IP1/JIP1 in organizing different components
CC of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or
CC MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a
CC functional multiprotein complex to ensure the effective activation of
CC the JNK signaling pathway. Regulates the differentiation of CD4(+) and
CC CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation.
CC Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells
CC and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial
CC role in the migration of neocortical neurons in the developing brain.
CC Controls proper cortical neuronal migration and the formation of
CC proximal cytoplasmic dilation in the leading process (PCDLP) in
CC migratory neocortical neurons by regulating the proper localization of
CC activated RAC1 and F-actin assembly (By similarity).
CC {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000269|PubMed:15659549,
CC ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164}.
CC -!- FUNCTION: (Microbial infection) Plays an essential role in the
CC targeting of HIV-1 Gag to the plasma membrane, this function is
CC dependent on it's RING domain, and hence it's E3 ligase activity.
CC {ECO:0000269|PubMed:15659549}.
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:0000269|PubMed:15659549,
CC ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with RAC1; in a GTP-dependent manner
CC (PubMed:20696164). 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. Interacts with HERP1. Probably part of a
CC signaling complex that may contain SH3RF1, MAPK8IP, DLK1, MAP2K4/MKK4,
CC MAP2K7/MKK7, MAPK8/JNK1, MAPK9/JNK2, AKT1 and AKT2 (PubMed:12514131,
CC PubMed:14504284, PubMed:16230351, PubMed:16571722, PubMed:17420289,
CC PubMed:17535800). 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. Interacts with SH3RF2 (By similarity).
CC {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000250|UniProtKB:Q71F54,
CC ECO:0000269|PubMed:12514131, ECO:0000269|PubMed:14504284,
CC ECO:0000269|PubMed:16230351, ECO:0000269|PubMed:16571722,
CC ECO:0000269|PubMed:17420289, ECO:0000269|PubMed:17535800,
CC ECO:0000269|PubMed:20696164}.
CC -!- INTERACTION:
CC Q7Z6J0; P63000: RAC1; NbExp=2; IntAct=EBI-311339, EBI-413628;
CC Q7Z6J0; O43255: SIAH2; NbExp=3; IntAct=EBI-311339, EBI-948141;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q71F54}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q69ZI1}. Golgi apparatus, trans-Golgi network
CC {ECO:0000269|PubMed:15659549, ECO:0000269|PubMed:17420289}.
CC Note=Colocalizes, with AKT2, in lamellipodia (By similarity).
CC Colocalizes, with HERP1, in trans-Golgi network.
CC {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000269|PubMed:17420289}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7Z6J0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z6J0-3; Sequence=VSP_033622, VSP_033623;
CC -!- DOMAIN: The RING finger domain is required for ubiquitin ligase
CC activity and autoubiquitination. {ECO:0000269|PubMed:20696164}.
CC -!- PTM: Phosphorylated at Ser-304 by AKT1 and AKT2. When phosphorylated,
CC it has reduced ability to bind Rac. {ECO:0000269|PubMed:17535800}.
CC -!- PTM: Autoubiquitinated (PubMed:20696164). Ubiquitinated by SH3RF2,
CC leading to proteasome-mediated degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q71F54, ECO:0000269|PubMed:20696164}.
CC -!- SIMILARITY: Belongs to the SH3RF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH33203.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH33203.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH53671.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the middle of the protein.; Evidence={ECO:0000305};
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DR EMBL; BC033203; AAH33203.1; ALT_SEQ; mRNA.
DR EMBL; BC041023; AAH41023.1; -; mRNA.
DR EMBL; BC053671; AAH53671.1; ALT_SEQ; mRNA.
DR EMBL; AK021429; BAB13822.1; -; mRNA.
DR EMBL; AB040927; BAA96018.1; -; mRNA.
DR CCDS; CCDS34099.1; -. [Q7Z6J0-1]
DR RefSeq; NP_065921.2; NM_020870.3. [Q7Z6J0-1]
DR PDB; 7NZC; X-ray; 1.11 A; AAA=135-194.
DR PDB; 7NZD; X-ray; 1.45 A; AAA=829-888.
DR PDBsum; 7NZC; -.
DR PDBsum; 7NZD; -.
DR AlphaFoldDB; Q7Z6J0; -.
DR SMR; Q7Z6J0; -.
DR BioGRID; 121673; 89.
DR CORUM; Q7Z6J0; -.
DR DIP; DIP-31636N; -.
DR ELM; Q7Z6J0; -.
DR IntAct; Q7Z6J0; 16.
DR MINT; Q7Z6J0; -.
DR STRING; 9606.ENSP00000284637; -.
DR GlyGen; Q7Z6J0; 4 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; Q7Z6J0; -.
DR PhosphoSitePlus; Q7Z6J0; -.
DR BioMuta; SH3RF1; -.
DR DMDM; 205830834; -.
DR EPD; Q7Z6J0; -.
DR jPOST; Q7Z6J0; -.
DR MassIVE; Q7Z6J0; -.
DR MaxQB; Q7Z6J0; -.
DR PaxDb; Q7Z6J0; -.
DR PeptideAtlas; Q7Z6J0; -.
DR PRIDE; Q7Z6J0; -.
DR ProteomicsDB; 69417; -. [Q7Z6J0-1]
DR ProteomicsDB; 69418; -. [Q7Z6J0-3]
DR ABCD; Q7Z6J0; 4 sequenced antibodies.
DR Antibodypedia; 28449; 156 antibodies from 24 providers.
DR DNASU; 57630; -.
DR Ensembl; ENST00000284637.14; ENSP00000284637.9; ENSG00000154447.15. [Q7Z6J0-1]
DR GeneID; 57630; -.
DR KEGG; hsa:57630; -.
DR MANE-Select; ENST00000284637.14; ENSP00000284637.9; NM_020870.4; NP_065921.2.
DR UCSC; uc003isa.2; human. [Q7Z6J0-1]
DR CTD; 57630; -.
DR DisGeNET; 57630; -.
DR GeneCards; SH3RF1; -.
DR HGNC; HGNC:17650; SH3RF1.
DR HPA; ENSG00000154447; Low tissue specificity.
DR MIM; 618642; gene.
DR neXtProt; NX_Q7Z6J0; -.
DR OpenTargets; ENSG00000154447; -.
DR PharmGKB; PA134915904; -.
DR VEuPathDB; HostDB:ENSG00000154447; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000155875; -.
DR HOGENOM; CLU_015769_1_0_1; -.
DR InParanoid; Q7Z6J0; -.
DR OMA; LVCERYR; -.
DR OrthoDB; 291531at2759; -.
DR PhylomeDB; Q7Z6J0; -.
DR TreeFam; TF105571; -.
DR PathwayCommons; Q7Z6J0; -.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q7Z6J0; -.
DR SIGNOR; Q7Z6J0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 57630; 11 hits in 1109 CRISPR screens.
DR ChiTaRS; SH3RF1; human.
DR GeneWiki; SH3RF1; -.
DR GenomeRNAi; 57630; -.
DR Pharos; Q7Z6J0; Tbio.
DR PRO; PR:Q7Z6J0; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q7Z6J0; protein.
DR Bgee; ENSG00000154447; Expressed in epithelial cell of pancreas and 180 other tissues.
DR ExpressionAtlas; Q7Z6J0; baseline and differential.
DR Genevisible; Q7Z6J0; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
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; IMP: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 CDD; cd11930; SH3_SH3RF1_2; 1.
DR CDD; cd11785; SH3_SH3RF_C; 1.
DR Gene3D; 3.30.40.10; -; 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 Pfam; PF00018; SH3_1; 1.
DR Pfam; PF14604; SH3_9; 3.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00184; RING; 1.
DR SMART; SM00326; SH3; 4.
DR SUPFAM; SSF50044; SSF50044; 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 3D-structure; Alternative splicing; Cell projection; Cytoplasm;
KW Golgi apparatus; Host-virus interaction; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..888
FT /note="E3 ubiquitin-protein ligase SH3RF1"
FT /id="PRO_0000334151"
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 445..506
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 829..888
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 108..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..362
FT /note="Interaction with RAC1"
FT /evidence="ECO:0000269|PubMed:20696164"
FT REGION 440..543
FT /note="Interaction with AKT2"
FT /evidence="ECO:0000250"
FT REGION 516..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 620..639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..741
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..321
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..541
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..706
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17535800,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q69ZI1"
FT VAR_SEQ 394..441
FT /note="TLNPPLPPPPLLAATVLASTPPGATAAAAAAGMGPRPMAGSTDQIAHL ->
FT APPPLLLLLEWDRGPWQDPLTRLHIYGRRLAPVCMLLYIHTLLGKRIN (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033622"
FT VAR_SEQ 442..888
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033623"
FT VARIANT 663
FT /note="P -> S (in dbSNP:rs3811813)"
FT /id="VAR_043342"
FT MUTAGEN 14
FT /note="V->A: Loss of Ubl activity."
FT /evidence="ECO:0000269|PubMed:17420289"
FT MUTAGEN 28
FT /note="C->A: Significant reduction in autoubiquitination;
FT when associated with A-30."
FT /evidence="ECO:0000269|PubMed:20696164"
FT MUTAGEN 30
FT /note="H->A: Significant reduction in autoubiquitination;
FT when associated with A-28."
FT /evidence="ECO:0000269|PubMed:20696164"
FT MUTAGEN 304
FT /note="S->A: Decreased level of phosphorylation and no
FT change in the ability to induce apoptosis."
FT /evidence="ECO:0000269|PubMed:17535800"
FT MUTAGEN 304
FT /note="S->D: Decreased level of phosphorylation and Rac-
FT binding ability and important loss of the ability to induce
FT apoptosis."
FT /evidence="ECO:0000269|PubMed:17535800"
FT MUTAGEN 304
FT /note="S->E: Decreased Rac-binding ability."
FT /evidence="ECO:0000269|PubMed:17535800"
SQ SEQUENCE 888 AA; 93129 MW; B3018000F03D0CF1 CRC64;
MDESALLDLL ECPVCLERLD ASAKVLPCQH TFCKRCLLGI VGSRNELRCP ECRTLVGSGV
EELPSNILLV RLLDGIKQRP WKPGPGGGSG TNCTNALRSQ SSTVANCSSK DLQSSQGGQQ
PRVQSWSPPV RGIPQLPCAK ALYNYEGKEP GDLKFSKGDI IILRRQVDEN WYHGEVNGIH
GFFPTNFVQI IKPLPQPPPQ CKALYDFEVK DKEADKDCLP FAKDDVLTVI RRVDENWAEG
MLADKIGIFP ISYVEFNSAA KQLIEWDKPP VPGVDAGECS SAAAQSSTAP KHSDTKKNTK
KRHSFTSLTM ANKSSQASQN RHSMEISPPV LISSSNPTAA ARISELSGLS CSAPSQVHIS
TTGLIVTPPP SSPVTTGPSF TFPSDVPYQA ALGTLNPPLP PPPLLAATVL ASTPPGATAA
AAAAGMGPRP MAGSTDQIAH LRPQTRPSVY VAIYPYTPRK EDELELRKGE MFLVFERCQD
GWFKGTSMHT SKIGVFPGNY VAPVTRAVTN ASQAKVPMST AGQTSRGVTM VSPSTAGGPA
QKLQGNGVAG SPSVVPAAVV SAAHIQTSPQ AKVLLHMTGQ MTVNQARNAV RTVAAHNQER
PTAAVTPIQV QNAAGLSPAS VGLSHHSLAS PQPAPLMPGS ATHTAAISIS RASAPLACAA
AAPLTSPSIT SASLEAEPSG RIVTVLPGLP TSPDSASSAC GNSSATKPDK DSKKEKKGLL
KLLSGASTKR KPRVSPPASP TLEVELGSAE LPLQGAVGPE LPPGGGHGRA GSCPVDGDGP
VTTAVAGAAL AQDAFHRKAS SLDSAVPIAP PPRQACSSLG PVLNESRPVV CERHRVVVSY
PPQSEAELEL KEGDIVFVHK KREDGWFKGT LQRNGKTGLF PGSFVENI
