SRMS_HUMAN
ID SRMS_HUMAN Reviewed; 488 AA.
AC Q9H3Y6;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Tyrosine-protein kinase Srms;
DE EC=2.7.10.2 {ECO:0000269|PubMed:23822091, ECO:0000269|PubMed:29496907};
GN Name=SRMS; Synonyms=C20orf148;
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 GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH DOK1,
RP DOMAIN, PHOSPHORYLATION AT TYR-380, AND MUTAGENESIS OF TRP-223; LYS-258 AND
RP TYR-380.
RX PubMed=23822091; DOI=10.1111/febs.12420;
RA Goel R.K., Miah S., Black K., Kalra N., Dai C., Lukong K.E.;
RT "The unique N-terminal region of SRMS regulates enzymatic activity and
RT phosphorylation of its novel substrate Dok1.";
RL FEBS J. 280:4539-4559(2013).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH KHDRBS1 AND VIM, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-258.
RX PubMed=29496907; DOI=10.1074/mcp.ra118.000643;
RA Goel R.K., Paczkowska M., Reimand J., Napper S., Lukong K.E.;
RT "Phosphoproteomics analysis identifies novel candidate substrates of the
RT non-receptor tyrosine kinase, SRMS.";
RL Mol. Cell. Proteomics 17:925-947(2018).
RN [4]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-73; ARG-75; VAL-88; LEU-301; GLU-377;
RP VAL-397; LEU-452; THR-453; LEU-457 AND THR-465.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase which phosphorylates
CC DOK1 on tyrosine residues (PubMed:23822091). Also phosphorylates
CC KHDRBS1/SAM68 and VIM on tyrosine residues (PubMed:29496907).
CC Phosphorylation of KHDRBS1 is EGF-dependent (PubMed:29496907).
CC {ECO:0000269|PubMed:23822091, ECO:0000269|PubMed:29496907}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:23822091, ECO:0000269|PubMed:29496907};
CC -!- SUBUNIT: Interacts (via the SH2 and SH3 domains) with DOK1
CC (PubMed:23822091). Interacts with KHDRBS1/SAM68 and VIM
CC (PubMed:29496907). {ECO:0000269|PubMed:23822091,
CC ECO:0000269|PubMed:29496907}.
CC -!- INTERACTION:
CC Q9H3Y6; Q99704: DOK1; NbExp=7; IntAct=EBI-8541270, EBI-1384360;
CC Q9H3Y6; O43639: NCK2; NbExp=3; IntAct=EBI-8541270, EBI-713635;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23822091,
CC ECO:0000269|PubMed:29496907}. Note=Localizes to punctate cytoplasmic
CC structures. {ECO:0000269|PubMed:23822091, ECO:0000269|PubMed:29496907}.
CC -!- TISSUE SPECIFICITY: Highly expressed in most breast cancers (at protein
CC level).
CC -!- DOMAIN: The N-terminal region regulates its kinase activity.
CC {ECO:0000269|PubMed:23822091}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AL121829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS13525.1; -.
DR RefSeq; NP_543013.1; NM_080823.3.
DR AlphaFoldDB; Q9H3Y6; -.
DR SMR; Q9H3Y6; -.
DR BioGRID; 112603; 28.
DR IntAct; Q9H3Y6; 16.
DR MINT; Q9H3Y6; -.
DR STRING; 9606.ENSP00000217188; -.
DR BindingDB; Q9H3Y6; -.
DR ChEMBL; CHEMBL5703; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9H3Y6; -.
DR iPTMnet; Q9H3Y6; -.
DR PhosphoSitePlus; Q9H3Y6; -.
DR BioMuta; SRMS; -.
DR DMDM; 27805732; -.
DR MassIVE; Q9H3Y6; -.
DR MaxQB; Q9H3Y6; -.
DR PaxDb; Q9H3Y6; -.
DR PeptideAtlas; Q9H3Y6; -.
DR PRIDE; Q9H3Y6; -.
DR ProteomicsDB; 80768; -.
DR Antibodypedia; 29781; 195 antibodies from 26 providers.
DR DNASU; 6725; -.
DR Ensembl; ENST00000217188.2; ENSP00000217188.1; ENSG00000125508.4.
DR GeneID; 6725; -.
DR KEGG; hsa:6725; -.
DR MANE-Select; ENST00000217188.2; ENSP00000217188.1; NM_080823.4; NP_543013.1.
DR UCSC; uc002yfi.3; human.
DR CTD; 6725; -.
DR DisGeNET; 6725; -.
DR GeneCards; SRMS; -.
DR HGNC; HGNC:11298; SRMS.
DR HPA; ENSG00000125508; Tissue enhanced (stomach).
DR MIM; 617797; gene.
DR neXtProt; NX_Q9H3Y6; -.
DR OpenTargets; ENSG00000125508; -.
DR PharmGKB; PA36122; -.
DR VEuPathDB; HostDB:ENSG00000125508; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000161518; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; Q9H3Y6; -.
DR OMA; RAQAKVC; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; Q9H3Y6; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; Q9H3Y6; -.
DR Reactome; R-HSA-8849472; PTK6 Down-Regulation.
DR SignaLink; Q9H3Y6; -.
DR SIGNOR; Q9H3Y6; -.
DR BioGRID-ORCS; 6725; 13 hits in 1106 CRISPR screens.
DR GenomeRNAi; 6725; -.
DR Pharos; Q9H3Y6; Tchem.
DR PRO; PR:Q9H3Y6; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H3Y6; protein.
DR Bgee; ENSG00000125508; Expressed in mucosa of transverse colon and 68 other tissues.
DR Genevisible; Q9H3Y6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0009968; P:negative regulation of signal transduction; TAS:Reactome.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..488
FT /note="Tyrosine-protein kinase Srms"
FT /id="PRO_0000088160"
FT DOMAIN 51..112
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 120..212
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 230..488
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 350
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 236..244
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 380
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23822091"
FT VARIANT 73
FT /note="R -> C (in dbSNP:rs56053583)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041831"
FT VARIANT 75
FT /note="G -> R (in dbSNP:rs55863722)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041832"
FT VARIANT 88
FT /note="I -> V (in dbSNP:rs35558836)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041833"
FT VARIANT 218
FT /note="P -> L (in dbSNP:rs378483)"
FT /id="VAR_051700"
FT VARIANT 255
FT /note="V -> M (in dbSNP:rs34969822)"
FT /id="VAR_051701"
FT VARIANT 301
FT /note="V -> L (in dbSNP:rs310657)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041834"
FT VARIANT 325
FT /note="P -> L (in dbSNP:rs8122355)"
FT /id="VAR_051702"
FT VARIANT 377
FT /note="D -> E (in dbSNP:rs55838540)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041835"
FT VARIANT 397
FT /note="A -> V (in dbSNP:rs6011889)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041836"
FT VARIANT 452
FT /note="P -> L (in dbSNP:rs8120713)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041837"
FT VARIANT 453
FT /note="A -> T (in dbSNP:rs310655)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041838"
FT VARIANT 457
FT /note="V -> L (in dbSNP:rs310654)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041839"
FT VARIANT 465
FT /note="S -> T (in dbSNP:rs33933649)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041840"
FT MUTAGEN 223
FT /note="W->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:23822091"
FT MUTAGEN 258
FT /note="K->M: Loss of kinase activity. Exhibits a diffused
FT cytoplasmic localization. No effect on interaction with
FT KHDRBS1 or VIM but abolishes tyrosine phosphorylation of
FT both substrates."
FT /evidence="ECO:0000269|PubMed:23822091,
FT ECO:0000269|PubMed:29496907"
FT MUTAGEN 380
FT /note="Y->F: Significant reduction in phosphorylation."
FT /evidence="ECO:0000269|PubMed:23822091"
SQ SEQUENCE 488 AA; 54507 MW; 83193AD26C5F6F68 CRC64;
MEPFLRRRLA FLSFFWDKIW PAGGEPDHGT PGSLDPNTDP VPTLPAEPCS PFPQLFLALY
DFTARCGGEL SVRRGDRLCA LEEGGGYIFA RRLSGQPSAG LVPITHVAKA SPETLSDQPW
YFSGVSRTQA QQLLLSPPNE PGAFLIRPSE SSLGGYSLSV RAQAKVCHYR VSMAADGSLY
LQKGRLFPGL EELLTYYKAN WKLIQNPLLQ PCMPQKAPRQ DVWERPHSEF ALGRKLGEGY
FGEVWEGLWL GSLPVAIKVI KSANMKLTDL AKEIQTLKGL RHERLIRLHA VCSGGEPVYI
VTELMRKGNL QAFLGTPEGR ALRLPPLLGF ACQVAEGMSY LEEQRVVHRD LAARNVLVDD
GLACKVADFG LARLLKDDIY SPSSSSKIPV KWTAPEAANY RVFSQKSDVW SFGVLLHEVF
TYGQCPYEGM TNHETLQQIM RGYRLPRPAA CPAEVYVLML ECWRSSPEER PSFATLREKL
HAIHRCHP
