SHC4_MOUSE
ID SHC4_MOUSE Reviewed; 626 AA.
AC Q6S5L9;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=SHC-transforming protein 4;
DE AltName: Full=Rai-like protein;
DE Short=RaLP;
DE AltName: Full=SHC-transforming protein D;
DE Short=mShcD;
DE AltName: Full=Src homology 2 domain-containing-transforming protein C4;
DE Short=SH2 domain protein C4;
GN Name=Shc4; Synonyms=Shcd;
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].
RC STRAIN=C57BL/6J;
RX PubMed=17409413; DOI=10.1158/0008-5472.can-06-2301;
RA Fagiani E., Giardina G., Luzi L., Cesaroni M., Quarto M., Capra M.,
RA Germano G., Bono M., Capillo M., Pelicci P., Lanfrancone L.;
RT "RaLP, a new member of the Src homology and collagen family, regulates cell
RT migration and tumor growth of metastatic melanomas.";
RL Cancer Res. 67:3064-3073(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP TISSUE SPECIFICITY, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17452444; DOI=10.1128/mcb.00184-07;
RA Jones N., Hardy W.R., Friese M.B., Jorgensen C., Smith M.J., Woody N.M.,
RA Burden S.J., Pawson T.;
RT "Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with
RT muscle-specific kinase.";
RL Mol. Cell. Biol. 27:4759-4773(2007).
CC -!- FUNCTION: Activates both Ras-dependent and Ras-independent migratory
CC pathways in melanomas. Contributes to the early phases of agrin-induced
CC tyrosine phosphorylation of CHRNB1. {ECO:0000269|PubMed:17452444}.
CC -!- SUBUNIT: Interacts (via PID domain) with phosphorylated MUSK (via NPXY
CC motif); undergoes tyrosine phosphorylation downstream of activated
CC MUSK. Interacts with GRB2; the interaction is dependent of Tyr-422
CC phosphorylation and increased by EGF (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000269|PubMed:17452444}. Note=Colocalized with MUSK at the
CC neuromuscular junction.
CC -!- TISSUE SPECIFICITY: Expressed in both brain and skeletal muscle; widely
CC expressed in brain namely olfactory bulb, cortex, hippocampus,
CC striatum, thalamus, and brain stem (at protein level). Only expressed
CC in melanomas. Weakly expressed in normal melanocytes and benign nevi.
CC Highly expressed at the transition from radial growth phase to vertical
CC growth phase and metastatic melanomas, when tumor cells acquire
CC migratory competence and invasive potential.
CC {ECO:0000269|PubMed:17452444}.
CC -!- PTM: Phosphorylated; the phosphorylation is enhanced by EGF.
CC Phosphorylation at Tyr-422 is required for the interaction with GRB2
CC (By similarity). {ECO:0000250}.
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DR EMBL; AY464564; AAR19362.1; -; mRNA.
DR EMBL; AL844580; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929166; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS16678.1; -.
DR RefSeq; NP_950187.1; NM_199022.2.
DR AlphaFoldDB; Q6S5L9; -.
DR SMR; Q6S5L9; -.
DR BioGRID; 234854; 1.
DR STRING; 10090.ENSMUSP00000043146; -.
DR iPTMnet; Q6S5L9; -.
DR PhosphoSitePlus; Q6S5L9; -.
DR MaxQB; Q6S5L9; -.
DR PaxDb; Q6S5L9; -.
DR PRIDE; Q6S5L9; -.
DR ProteomicsDB; 257223; -.
DR Antibodypedia; 24605; 175 antibodies from 30 providers.
DR DNASU; 271849; -.
DR Ensembl; ENSMUST00000042246; ENSMUSP00000043146; ENSMUSG00000035109.
DR GeneID; 271849; -.
DR KEGG; mmu:271849; -.
DR UCSC; uc008mcv.1; mouse.
DR CTD; 399694; -.
DR MGI; MGI:2655364; Shc4.
DR VEuPathDB; HostDB:ENSMUSG00000035109; -.
DR eggNOG; KOG3697; Eukaryota.
DR GeneTree; ENSGT00950000182870; -.
DR HOGENOM; CLU_029532_2_0_1; -.
DR InParanoid; Q6S5L9; -.
DR OMA; LMNIDNQ; -.
DR OrthoDB; 1351843at2759; -.
DR PhylomeDB; Q6S5L9; -.
DR TreeFam; TF315807; -.
DR BioGRID-ORCS; 271849; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Shc4; mouse.
DR PRO; PR:Q6S5L9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q6S5L9; protein.
DR Bgee; ENSMUSG00000035109; Expressed in sciatic nerve and 126 other tissues.
DR ExpressionAtlas; Q6S5L9; baseline and differential.
DR Genevisible; Q6S5L9; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd01209; PTB_Shc; 1.
DR CDD; cd09925; SH2_SHC; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006019; PID_Shc-like.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR029596; SHC4.
DR InterPro; IPR035676; SHC_SH2.
DR PANTHER; PTHR10337:SF12; PTHR10337:SF12; 1.
DR Pfam; PF00640; PID; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00629; SHCPIDOMAIN.
DR SMART; SM00462; PTB; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Membrane; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; SH2 domain; Synapse.
FT CHAIN 1..626
FT /note="SHC-transforming protein 4"
FT /id="PRO_0000337201"
FT DOMAIN 186..369
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 522..613
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..185
FT /note="CH2"
FT REGION 38..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..521
FT /note="CH1"
FT COMPBIAS 38..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..139
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..175
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 422
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q6S5L8"
SQ SEQUENCE 626 AA; 68519 MW; 031D64EA64D8F0FE CRC64;
MRERSQDSQA GLTLYVGLFG HLGMLHRTKY SRFRNESITS LDEGSPGGSV GNKGSSPPPY
PALAPHLPTE DATVSSQESP TALCTLIPRM ASMKLANPIT FLGLKTFCLG TKQVSRLKLQ
ENQDQTPSRP ASPESNLNRT GPAPAPDPDQ VGRRPTSLRP DTCPLPGPGE PSPRSKQDGP
PLQHLLGNGL NYCVRYMGCI EVLQSMRSLD FGMRTQVTRE AISRLCEAVP GAHGAIKKRK
APVKFLTTVL GKSNLQFSGM NIKLTVSTSS LTLMNLDNQQ IIANHQMQSI SFASGGDPDT
TDYVAYVAKD PVNQRACHIL ECRSGMAQDV ISTIGQAFEL RFKQYLKNPS LNTWEREEVL
VDGAPEDRDH DYYNSIPGKQ PPEGGISDVR IQAQATDQMA YCPIRCEKLC YLPGNSTCSG
VYKNCMGRSR PIGIPHERAG QGDTPSLRHF WRVDLFDDPC YVNTQALQSM HSYAGNQSSA
LPQGSPWHLG KAPETVQPGA TAKPGSALAL PHIRQQLWDE ECFHGKLSRG AAEKLLVKDG
DFLVRESVTS PGQFVLSGLQ GGQAKHLLLV DPEGKVRTKD HVFDNVGHLI KYHMDNNLPI
ISSGSEVRLK QPIRKYDNTG LLPPKK
