SRPX2_HUMAN
ID SRPX2_HUMAN Reviewed; 465 AA.
AC O60687; B3KQT3; Q8WW85;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Sushi repeat-containing protein SRPX2;
DE AltName: Full=Sushi-repeat protein upregulated in leukemia;
DE Flags: Precursor;
GN Name=SRPX2; Synonyms=SRPUL;
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 [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Leukemia;
RX PubMed=9864177;
RA Kurosawa H., Goi K., Inukai T., Inaba T., Chang K.S., Shinjyo T.,
RA Rakestraw K.M., Naeve C.W., Look A.T.;
RT "Two candidate downstream target genes for E2A-HLF.";
RL Blood 93:321-332(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang C.-H., Chen H., Peng J., Chen Y.;
RT "Cloning and characterization of the sushi-repeat containing protein (SRP)
RT as a novel interaction partner of Rh type C glycoprotein (RhCG).";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-287.
RC TISSUE=Placenta;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS RESDX SER-72
RP AND SER-327, AND CHARACTERIZATION OF VARIANTS RESDX SER-72 AND SER-327.
RX PubMed=16497722; DOI=10.1093/hmg/ddl035;
RA Roll P., Rudolf G., Pereira S., Royer B., Scheffer I.E., Massacrier A.,
RA Valenti M.-P., Roeckel-Trevisiol N., Jamali S., Beclin C., Seegmuller C.,
RA Metz-Lutz M.-N., Lemainque A., Delepine M., Caloustian C.,
RA de Saint Martin A., Bruneau N., Depetris D., Mattei M.-G., Flori E.,
RA Robaglia-Schlupp A., Levy N., Neubauer B.A., Ravid R., Marescaux C.,
RA Berkovic S.F., Hirsch E., Lathrop M., Cau P., Szepetowski P.;
RT "SRPX2 mutations in disorders of language cortex and cognition.";
RL Hum. Mol. Genet. 15:1195-1207(2006).
RN [7]
RP FUNCTION, INTERACTION WITH ADAMTS4; CTSB AND PLAUR, AND TISSUE SPECIFICITY.
RX PubMed=18718938; DOI=10.1093/hmg/ddn256;
RA Royer-Zemmour B., Ponsole-Lenfant M., Gara H., Roll P., Leveque C.,
RA Massacrier A., Ferracci G., Cillario J., Robaglia-Schlupp A.,
RA Vincentelli R., Cau P., Szepetowski P.;
RT "Epileptic and developmental disorders of the speech cortex:
RT ligand/receptor interaction of wild-type and mutant SRPX2 with the
RT plasminogen activator receptor uPAR.";
RL Hum. Mol. Genet. 17:3617-3630(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19065654; DOI=10.1002/ijc.24065;
RA Tanaka K., Arao T., Maegawa M., Matsumoto K., Kaneda H., Kudo K.,
RA Fujita Y., Yokote H., Yanagihara K., Yamada Y., Okamoto I., Nakagawa K.,
RA Nishio K.;
RT "SRPX2 is overexpressed in gastric cancer and promotes cellular migration
RT and adhesion.";
RL Int. J. Cancer 124:1072-1080(2009).
RN [9]
RP INTERACTION WITH HGF, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP GLYCOSYLATION.
RX PubMed=22242148; DOI=10.1371/journal.pone.0027922;
RA Tanaka K., Arao T., Tamura D., Aomatsu K., Furuta K., Matsumoto K.,
RA Kaneda H., Kudo K., Fujita Y., Kimura H., Yanagihara K., Yamada Y.,
RA Okamoto I., Nakagawa K., Nishio K.;
RT "SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in
RT gastrointestinal cancer.";
RL PLoS ONE 7:E27922-E27922(2012).
RN [10]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=24179158; DOI=10.1126/science.1245079;
RA Sia G.M., Clem R.L., Huganir R.L.;
RT "The human language-associated gene SRPX2 regulates synapse formation and
RT vocalization in mice.";
RL Science 342:987-991(2013).
CC -!- FUNCTION: Acts as a ligand for the urokinase plasminogen activator
CC surface receptor. Plays a role in angiogenesis by inducing endothelial
CC cell migration and the formation of vascular network (cords). Involved
CC in cellular migration and adhesion. Increases the phosphorylation
CC levels of FAK. Interacts with and increases the mitogenic activity of
CC HGF. Promotes synapse formation. May have a role in the perisylvian
CC region, critical for language and cognitive development.
CC {ECO:0000269|PubMed:16497722, ECO:0000269|PubMed:18718938,
CC ECO:0000269|PubMed:19065654, ECO:0000269|PubMed:24179158}.
CC -!- SUBUNIT: Forms homooligomers (By similarity). Interacts with PLAUR (via
CC the UPAR/Ly6 domains), ADAMTS4 and CTSB. Interacts with HGF; the
CC interaction increases the mitogenic activity of HGF. {ECO:0000250,
CC ECO:0000269|PubMed:18718938, ECO:0000269|PubMed:22242148,
CC ECO:0000269|PubMed:24179158}.
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cell surface. Synapse
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in neurons of the rolandic area of the
CC brain (at protein level). Highly expressed in the brain, placenta,
CC lung, trachea, uterus, adrenal gland, heart, ovary and placenta. Weakly
CC expressed in the peripheral blood, brain and bone marrow. Expressed in
CC numerous cancer cell lines and in gastrointestinal cancer cells. Higher
CC levels found in colorectal cancers than in normal colonic mucosa.
CC {ECO:0000269|PubMed:16497722, ECO:0000269|PubMed:18718938,
CC ECO:0000269|PubMed:19065654, ECO:0000269|PubMed:22242148,
CC ECO:0000269|PubMed:9864177}.
CC -!- PTM: Contains chondroitin sulfate chains.
CC -!- DISEASE: Rolandic epilepsy, impaired intellectual development, and
CC speech dyspraxia, X-linked (RESDX) [MIM:300643]: A condition
CC characterized by the association of rolandic seizures with oral and
CC speech dyspraxia, and intellectual disability. Rolandic seizures occur
CC during a period of significant brain maturation. During this time,
CC dysfunction of neural network activities such as focal discharges may
CC be associated with specific developmental disabilities resulting in
CC specific cognitive impairments of language, visuo-spatial abilities or
CC attention. {ECO:0000269|PubMed:16497722}. Note=The disease may be
CC caused by variants affecting the gene represented in this entry.
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DR EMBL; AF060567; AAC15765.1; -; mRNA.
DR EMBL; AF393649; AAM73693.1; -; mRNA.
DR EMBL; AK075462; BAG52145.1; -; mRNA.
DR EMBL; AL035608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390040; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020733; AAH20733.1; -; mRNA.
DR CCDS; CCDS14471.1; -.
DR RefSeq; NP_055282.1; NM_014467.2.
DR AlphaFoldDB; O60687; -.
DR BioGRID; 118110; 1.
DR IntAct; O60687; 2.
DR STRING; 9606.ENSP00000362095; -.
DR iPTMnet; O60687; -.
DR PhosphoSitePlus; O60687; -.
DR BioMuta; SRPX2; -.
DR EPD; O60687; -.
DR jPOST; O60687; -.
DR MassIVE; O60687; -.
DR PaxDb; O60687; -.
DR PeptideAtlas; O60687; -.
DR PRIDE; O60687; -.
DR ProteomicsDB; 49528; -.
DR Antibodypedia; 28519; 174 antibodies from 31 providers.
DR DNASU; 27286; -.
DR Ensembl; ENST00000373004.5; ENSP00000362095.3; ENSG00000102359.9.
DR GeneID; 27286; -.
DR KEGG; hsa:27286; -.
DR MANE-Select; ENST00000373004.5; ENSP00000362095.3; NM_014467.3; NP_055282.1.
DR UCSC; uc004egb.4; human.
DR CTD; 27286; -.
DR DisGeNET; 27286; -.
DR GeneCards; SRPX2; -.
DR HGNC; HGNC:30668; SRPX2.
DR HPA; ENSG00000102359; Tissue enhanced (adipose).
DR MalaCards; SRPX2; -.
DR MIM; 300642; gene.
DR MIM; 300643; phenotype.
DR neXtProt; NX_O60687; -.
DR OpenTargets; ENSG00000102359; -.
DR Orphanet; 98889; Bilateral perisylvian polymicrogyria.
DR Orphanet; 1945; Rolandic epilepsy.
DR Orphanet; 163721; Rolandic epilepsy-speech dyspraxia syndrome.
DR PharmGKB; PA134983994; -.
DR VEuPathDB; HostDB:ENSG00000102359; -.
DR eggNOG; ENOG502QREP; Eukaryota.
DR GeneTree; ENSGT00940000159149; -.
DR HOGENOM; CLU_047011_0_0_1; -.
DR InParanoid; O60687; -.
DR OMA; EQRDMCE; -.
DR OrthoDB; 544541at2759; -.
DR PhylomeDB; O60687; -.
DR TreeFam; TF336515; -.
DR PathwayCommons; O60687; -.
DR SignaLink; O60687; -.
DR BioGRID-ORCS; 27286; 14 hits in 694 CRISPR screens.
DR GeneWiki; SRPX2; -.
DR GenomeRNAi; 27286; -.
DR Pharos; O60687; Tbio.
DR PRO; PR:O60687; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O60687; protein.
DR Bgee; ENSG00000102359; Expressed in stromal cell of endometrium and 137 other tissues.
DR ExpressionAtlas; O60687; baseline and differential.
DR Genevisible; O60687; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0060076; C:excitatory synapse; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0097060; C:synaptic membrane; ISS:UniProtKB.
DR GO; GO:0036458; F:hepatocyte growth factor binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0048870; P:cell motility; IDA:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; IDA:UniProtKB.
DR GO; GO:0071625; P:vocalization behavior; IEA:Ensembl.
DR CDD; cd00033; CCP; 3.
DR InterPro; IPR025232; DUF4174.
DR InterPro; IPR003410; HYR_dom.
DR InterPro; IPR043555; SRPX-like.
DR InterPro; IPR028768; SRPX2.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR PANTHER; PTHR46343; PTHR46343; 1.
DR PANTHER; PTHR46343:SF3; PTHR46343:SF3; 1.
DR Pfam; PF13778; DUF4174; 1.
DR Pfam; PF02494; HYR; 1.
DR Pfam; PF00084; Sushi; 3.
DR SMART; SM00032; CCP; 3.
DR SUPFAM; SSF57535; SSF57535; 3.
DR PROSITE; PS50825; HYR; 1.
DR PROSITE; PS50923; SUSHI; 3.
PE 1: Evidence at protein level;
KW Angiogenesis; Cell adhesion; Cytoplasm; Disease variant; Disulfide bond;
KW Epilepsy; Glycoprotein; Intellectual disability; Proteoglycan;
KW Reference proteome; Repeat; Secreted; Signal; Sushi; Synapse.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..465
FT /note="Sushi repeat-containing protein SRPX2"
FT /id="PRO_0000274525"
FT DOMAIN 69..119
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 120..178
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 177..261
FT /note="HYR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00113"
FT DOMAIN 262..321
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 71..105
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 91..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 122..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 149..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 264..306
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 292..319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VARIANT 72
FT /note="Y -> S (in RESDX; unknown pathological significance;
FT affects intracellular processing; increases the interaction
FT with PLAUR; dbSNP:rs121918364)"
FT /evidence="ECO:0000269|PubMed:16497722"
FT /id="VAR_030312"
FT VARIANT 287
FT /note="T -> S (in dbSNP:rs17851822)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030313"
FT VARIANT 327
FT /note="N -> S (in RESDX; unknown pathological significance;
FT results in a gain of glycosylation; affects intracellular
FT processing; does not affect interaction with PLAUR;
FT dbSNP:rs121918363)"
FT /evidence="ECO:0000269|PubMed:16497722"
FT /id="VAR_030314"
SQ SEQUENCE 465 AA; 52972 MW; 4D752B187FF3EFB8 CRC64;
MASQLTQRGA LFLLFFLTPA VTPTWYAGSG YYPDESYNEV YAEEVPQAPA LDYRVPRWCY
TLNIQDGEAT CYSPKGGNYH SSLGTRCELS CDRGFRLIGR RSVQCLPSRR WSGTAYCRQM
RCHALPFITS GTYTCTNGVL LDSRCDYSCS SGYHLEGDRS RICMEDGRWS GGEPVCVDID
PPKIRCPHSR EKMAEPEKLT ARVYWDPPLV KDSADGTITR VTLRGPEPGS HFPEGEHVIR
YTAYDRAYNR ASCKFIVKVQ VRRCPTLKPP QHGYLTCTSA GDNYGATCEY HCDGGYDRQG
TPSRVCQSSR QWSGSPPICA PMKINVNVNS AAGLLDQFYE KQRLLIISAP DPSNRYYKMQ
ISMLQQSTCG LDLRHVTIIE LVGQPPQEVG RIREQQLSAN IIEELRQFQR LTRSYFNMVL
IDKQGIDRDR YMEPVTPEEI FTFIDDYLLS NQELTQRREQ RDICE
