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 27-NOV-2024, entry version 175. 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 {ECO:0000269|PubMed:22242148}. CC Cytoplasm. Cell surface. Synapse {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 {ECO:0000269|PubMed:22242148}. 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyGen; O60687; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O60687; -. DR PhosphoSitePlus; O60687; -. DR BioMuta; SRPX2; -. DR jPOST; O60687; -. DR MassIVE; O60687; -. DR PaxDb; 9606-ENSP00000362095; -. DR PeptideAtlas; O60687; -. DR ProteomicsDB; 49528; -. DR Antibodypedia; 28519; 172 antibodies from 30 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 AGR; HGNC:30668; -. 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; 163721; Rolandic epilepsy-speech dyspraxia syndrome. DR Orphanet; 1945; Self-limited epilepsy with centrotemporal spikes. 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; 5406861at2759; -. DR PhylomeDB; O60687; -. DR TreeFam; TF336515; -. DR PathwayCommons; O60687; -. DR SignaLink; O60687; -. DR BioGRID-ORCS; 27286; 14 hits in 766 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 139 other cell types or tissues. DR ExpressionAtlas; O60687; baseline and differential. 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:0098978; C:glutamatergic synapse; IEA:Ensembl. 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 FunFam; 2.10.70.10:FF:000024; Sushi repeat-containing protein SRPX; 1. DR FunFam; 2.10.70.10:FF:000073; Sushi repeat-containing protein SRPX2; 1. DR FunFam; 2.10.70.10:FF:000058; sushi repeat-containing protein SRPX2; 1. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 3. DR InterPro; IPR025232; DUF4174. DR InterPro; IPR003410; HYR_dom. DR InterPro; IPR043555; SRPX-like. DR InterPro; IPR035976; Sushi/SCR/CCP_sf. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR PANTHER; PTHR46343; HYR DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR46343:SF3; SUSHI REPEAT-CONTAINING PROTEIN SRPX2; 1. DR Pfam; PF13778; DUF4174; 1. DR Pfam; PF02494; HYR; 1. DR Pfam; PF00084; Sushi; 3. DR SMART; SM00032; CCP; 3. DR SUPFAM; SSF57535; Complement control module/SCR domain; 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 Proteomics identification; Reference proteome; Repeat; Secreted; Signal; KW 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; uncertain significance; affects FT intracellular processing; increases the interaction with FT 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; uncertain significance; results in FT a gain of glycosylation; affects intracellular processing; FT does not affect interaction with PLAUR; 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 //