ID SH3R1_MOUSE Reviewed; 892 AA.
AC Q69ZI1; O70254; Q3UG42; Q6P9M8; Q8BR66; Q8C2T5;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 27-MAR-2024, entry version 133.
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 {ECO:0000303|PubMed:22959435, ECO:0000303|PubMed:27084103};
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 {ECO:0000303|PubMed:22959435,
GN ECO:0000303|PubMed:27084103}, Posh1 {ECO:0000250|UniProtKB:Q7Z6J0}, Sh3md2;
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), FUNCTION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH RAC1.
RX PubMed=9482736; DOI=10.1093/emboj/17.5.1395;
RA Tapon N., Nagata K., Lamarche N., Hall A.;
RT "A new rac target POSH is an SH3-containing scaffold protein involved in
RT the JNK and NF-kappaB signalling pathways.";
RL EMBO J. 17:1395-1404(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Embryonic tail;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 200-892 (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Corpora quadrigemina, and Thymus;
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] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 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 [6]
RP INTERACTION WITH AKT2, MUTAGENESIS OF GLU-470 AND TRP-489, AND SUBCELLULAR
RP LOCATION.
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 [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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304 AND SER-741, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAC1, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=22959435; DOI=10.1016/j.celrep.2012.08.007;
RA Yang T., Sun Y., Zhang F., Zhu Y., Shi L., Li H., Xu Z.;
RT "POSH localizes activated Rac1 to control the formation of cytoplasmic
RT dilation of the leading process and neuronal migration.";
RL Cell Rep. 2:640-651(2012).
RN [11]
RP FUNCTION, INTERACTION WITH MAPK8IP1, AND IDENTIFICATION IN A COMPLEX WITH
RP RAC1; MAP3K11; MAP2K7; MAPK8IP1 AND MAPK8.
RX PubMed=23963642; DOI=10.1002/eji.201343635;
RA Cunningham C.A., Knudson K.M., Peng B.J., Teixeiro E., Daniels M.A.;
RT "The POSH/JIP-1 scaffold network regulates TCR-mediated JNK1 signals and
RT effector function in CD8(+) T cells.";
RL Eur. J. Immunol. 43:3361-3371(2013).
RN [12]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAC2; MAP3K7; MAP2K7;
RP MAPK8IP1; MAPK8 AND MAPK9.
RX PubMed=27084103; DOI=10.4049/jimmunol.1501728;
RA Cunningham C.A., Cardwell L.N., Guan Y., Teixeiro E., Daniels M.A.;
RT "POSH regulates CD4+ T cell differentiation and survival.";
RL J. Immunol. 196:4003-4013(2016).
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 its 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. Regulates the differentiation
CC of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell
CC differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2
CC in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells
CC (PubMed:23963642, PubMed:27084103, PubMed:9482736). 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 (PubMed:22959435).
CC {ECO:0000250|UniProtKB:Q7Z6J0, ECO:0000269|PubMed:22959435,
CC ECO:0000269|PubMed:23963642, ECO:0000269|PubMed:27084103,
CC ECO:0000269|PubMed:9482736}.
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 (By similarity). Interacts with RAC1; in
CC a GTP-dependent manner (PubMed:22959435, PubMed:9482736). Interacts
CC with MAP3K10/MLK2 and MAP3K11/MLK3. Interacts with MAPK8IP; this
CC interaction leads to the PJAC complex (POSH-JIP or SH3RF1/MAPK8IP1
CC apoptotic complex) with a 1:1 ratio. Interacts with SIAH1. Probably
CC part of a signaling complex that may contain SH3RF1, MAPK8IP, DLK1,
CC MAP2K4/MKK4, MAP2K7/MKK7, MAPK8/JNK1, MAPK9/JNK2, AKT1 and AKT2
CC (PubMed:12514131, PubMed:14504284, PubMed:16230351, PubMed:16571722,
CC PubMed:23963642). Found in a complex with RAC2, MAP3K7/TAK1,
CC MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2
CC (PubMed:27084103). Found in a complex with RAC1, MAP3K11/MLK3,
CC MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642). Interacts
CC with SH3RF2 (By similarity). {ECO:0000250|UniProtKB:Q71F54,
CC ECO:0000250|UniProtKB:Q7Z6J0, ECO:0000269|PubMed:12514131,
CC ECO:0000269|PubMed:14504284, ECO:0000269|PubMed:16230351,
CC ECO:0000269|PubMed:16571722, ECO:0000269|PubMed:22959435,
CC ECO:0000269|PubMed:23963642, ECO:0000269|PubMed:27084103,
CC ECO:0000269|PubMed:9482736}.
CC -!- INTERACTION:
CC Q69ZI1; Q9Z2F7: Bnip3l; NbExp=4; IntAct=EBI-957380, EBI-1774669;
CC Q69ZI1; Q8IUQ4: SIAH1; Xeno; NbExp=5; IntAct=EBI-957380, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q71F54}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:14504284, ECO:0000269|PubMed:22959435}. Golgi
CC apparatus, trans-Golgi network {ECO:0000269|PubMed:14504284}.
CC Note=Colocalizes, with AKT2 in lamellipodia. Colocalizes, with HERP1,
CC in trans-Golgi network (By similarity). {ECO:0000250|UniProtKB:Q7Z6J0,
CC ECO:0000269|PubMed:14504284}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q69ZI1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q69ZI1-2; Sequence=VSP_033624;
CC Name=3;
CC IsoId=Q69ZI1-3; Sequence=VSP_033627, VSP_033628;
CC Name=4;
CC IsoId=Q69ZI1-4; Sequence=VSP_033625, VSP_033626;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:9482736}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryonic brain. Expressed
CC strongly in the venricular zone (VZ), subventricular zone (SVZ), and
CC lower intermediate zone (IZ) but weakly in the upper IZ and cortical
CC plate (CP) at 14.5 dpc. At 16.5 dpc, expression increases in the IZ and
CC CP. At 18.5 dpc, it increases significantly in the CP but decreases in
CC the IZ, SVZ, and VZ (at protein level). {ECO:0000269|PubMed:22959435}.
CC -!- DOMAIN: The RING finger domain is required for ubiquitin ligase
CC activity and autoubiquitination. {ECO:0000250|UniProtKB:Q7Z6J0}.
CC -!- PTM: Phosphorylated at Ser-304 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:0000250|UniProtKB:Q71F54}.
CC -!- SIMILARITY: Belongs to the SH3RF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32463.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF030131; AAC40070.1; -; mRNA.
DR EMBL; AK173185; BAD32463.1; ALT_INIT; mRNA.
DR EMBL; BC060113; AAH60113.1; -; mRNA.
DR EMBL; BC060696; AAH60696.1; -; mRNA.
DR EMBL; AK088003; BAC40088.1; -; mRNA.
DR EMBL; AK045470; BAC32385.1; -; mRNA.
DR EMBL; AK148137; BAE28367.1; -; mRNA.
DR PIR; T09071; T09071.
DR RefSeq; NP_067481.2; NM_021506.2.
DR AlphaFoldDB; Q69ZI1; -.
DR SMR; Q69ZI1; -.
DR BioGRID; 208480; 7.
DR IntAct; Q69ZI1; 6.
DR STRING; 10090.ENSMUSP00000034060; -.
DR GlyGen; Q69ZI1; 7 sites, 1 O-linked glycan (7 sites).
DR iPTMnet; Q69ZI1; -.
DR PhosphoSitePlus; Q69ZI1; -.
DR MaxQB; Q69ZI1; -.
DR PaxDb; 10090-ENSMUSP00000034060; -.
DR ProteomicsDB; 261345; -. [Q69ZI1-1]
DR ProteomicsDB; 261346; -. [Q69ZI1-2]
DR ProteomicsDB; 261347; -. [Q69ZI1-3]
DR ProteomicsDB; 261348; -. [Q69ZI1-4]
DR Pumba; Q69ZI1; -.
DR DNASU; 59009; -.
DR GeneID; 59009; -.
DR KEGG; mmu:59009; -.
DR AGR; MGI:1913066; -.
DR CTD; 57630; -.
DR MGI; MGI:1913066; Sh3rf1.
DR eggNOG; KOG2177; Eukaryota.
DR InParanoid; Q69ZI1; -.
DR OrthoDB; 5407056at2759; -.
DR PhylomeDB; Q69ZI1; -.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 59009; 1 hit in 78 CRISPR screens.
DR ChiTaRS; Sh3rf1; mouse.
DR PRO; PR:Q69ZI1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q69ZI1; Protein.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP: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; IMP:UniProtKB.
DR GO; GO:2000564; P:regulation of CD8-positive, alpha-beta T cell proliferation; IMP:UniProtKB.
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 Alternative splicing; Cell projection; Cytoplasm; Golgi apparatus;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; SH3 domain;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..892
FT /note="E3 ubiquitin-protein ligase SH3RF1"
FT /id="PRO_0000334152"
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 452..513
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 833..892
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 292..362
FT /note="Interaction with RAC1"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6J0"
FT REGION 447..550
FT /note="Interaction with AKT2"
FT /evidence="ECO:0000269|PubMed:14504284"
FT REGION 532..555
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 688..751
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 691..708
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 539
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6J0"
FT MOD_RES 741
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 160..189
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033624"
FT VAR_SEQ 345..381
FT /note="ELSGLSCSAPSQVHISTTGLIVTPPPSSPVTTGPAFT -> APSQVQGRGQL
FT PKRGLLTSGKILAASFIFALVTSSLL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033625"
FT VAR_SEQ 382..892
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033626"
FT VAR_SEQ 788..828
FT /note="AAGTAALAQDAFHRKTSSLDSAVPIAPPPRQACSSLGPVMN -> DRWNSSP
FT SPGCLPPQDKLPGLRSAHCSTTSPGLLLPGPSHE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033627"
FT VAR_SEQ 829..892
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033628"
FT MUTAGEN 470
FT /note="E->Q: Loss of binding to AKT2."
FT /evidence="ECO:0000269|PubMed:14504284"
FT MUTAGEN 489
FT /note="W->A: Loss of binding to AKT2 and enhanced binding
FT to MAP3K11."
FT /evidence="ECO:0000269|PubMed:14504284"
FT CONFLICT 160
FT /note="I -> T (in Ref. 1; AAC40070)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="R -> S (in Ref. 3; BAE28367)"
FT /evidence="ECO:0000305"
FT CONFLICT 342
FT /note="R -> G (in Ref. 3; BAE28367)"
FT /evidence="ECO:0000305"
FT CONFLICT 431
FT /note="Missing (in Ref. 3; BAC32385 and 4; AAH60113/
FT AAH60696)"
FT /evidence="ECO:0000305"
FT CONFLICT 630
FT /note="L -> M (in Ref. 3; BAE28367)"
FT /evidence="ECO:0000305"
FT CONFLICT 679
FT /note="M -> V (in Ref. 3; BAC32385 and 4; AAH60113/
FT AAH60696)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 892 AA; 93447 MW; D92071116F4D6EBE CRC64;
MDESALLDLL ECPVCLERLD ASAKVLPCQH TFCKRCLLGI VGSRNELRCP ECRTLVGSGV
DELPSNILLV RLLDGIKQRP WKPGPGGGGG TTCTNTLRAQ GSTVVNCGSK DLQSSQCGQQ
PRVQAWSPPV RGIPQLPCAK ALYNYEGKEP GDLKFSKGDI IILRRQVDEN WYHGEVSGVH
GFFPTNFVQI IKPLPQPPPQ CKALYDFEVK DKEADKDCLP FAKDDVLTVI RRVDENWAEG
MLADKIGIFP ISYVEFNSAA KQLIEWDKPP VPGVDTAECP SATAQSTSAS KHPDTKKNTR
KRHSFTSLTM ANKSSQGSQN RHSMEISPPV LISSSNPTAA ARISELSGLS CSAPSQVHIS
TTGLIVTPPP SSPVTTGPAF TFPSDVPYQA ALGSMNPPLP PPPLLAATVL ASTPSGATAA
VAAAAAAAAA AGMGPRPVMG SSEQIAHLRP QTRPSVYVAI YPYTPRKEDE LELRKGEMFL
VFERCQDGWY KGTSMHTSKI GVFPGNYVAP VTRAVTNASQ AKVSMSTAGQ ASRGVTMVSP
STAGGPTQKP QGNGVAGNPS VVPTAVVSAA HIQTSPQAKV LLHMSGQMTV NQARNAVRTV
AAHSQERPTA AVTPIQVQNA ACLGPASVGL PHHSLASQPL PPMAGPAAHG AAVSISRTNA
PMACAAGASL ASPNMTSAML ETEPSGRTVT ILPGLPTSPE SAASACGNSS AGKPDKDSKK
EKKGLLKLLS GASTKRKPRV SPPASPTLDV ELGAGEAPLQ GAVGPELPLG GSHGRVGSCP
TDGDGPVAAG TAALAQDAFH RKTSSLDSAV PIAPPPRQAC SSLGPVMNEA RPVVCERHRV
VVSYPPQSEA ELELKEGDIV FVHKKREDGW FKGTLQRNGK TGLFPGSFVE NI
//
