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   13-FEB-2019, entry version 145.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE
RP   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
RT   (SRP) as a novel interaction partner of Rh type C glycoprotein
RT   (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-
RT   length human cDNAs encoding secretion or membrane proteins from oligo-
RT   capped cDNA 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.,
RA   Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA   Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA   Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA   Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA   Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA   Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA   Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA   Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA   Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA   Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA   Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA   Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA   Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA   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.,
RA   Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA   Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA   Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA   Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA   Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA   Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA   Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA   Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA   Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA   de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA   Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA   Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA   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.,
RA   Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA   Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA   Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA   Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA   Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA   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.,
RA   Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA   Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA   Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA   Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA   Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA   Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA   Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA   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.,
RA   Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA   Gibbs R.A., Beck S., 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS RESDX
RP   SER-72 AND SER-327, AND CHARACTERIZATION OF VARIANTS RESDX SER-72 AND
RP   SER-327.
RX   PubMed=16497722; DOI=10.1093/hmg/ddl035;
RA   Roll P., Rudolf G., Pereira S., Royer B., Scheffer I.E.,
RA   Massacrier A., Valenti M.-P., Roeckel-Trevisiol N., Jamali S.,
RA   Beclin C., Seegmuller C., Metz-Lutz M.-N., Lemainque A., Delepine M.,
RA   Caloustian C., de Saint Martin A., Bruneau N., Depetris D.,
RA   Mattei M.-G., Flori E., Robaglia-Schlupp A., Levy N., Neubauer B.A.,
RA   Ravid R., Marescaux C., Berkovic S.F., Hirsch E., Lathrop M., Cau P.,
RA   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
RP   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.,
RA   Nakagawa K., Nishio K.;
RT   "SRPX2 is overexpressed in gastric cancer and promotes cellular
RT   migration 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
RT   overexpressed in 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
RT   and 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
CC       endothelial cell migration and the formation of vascular network
CC       (cords). Involved in cellular migration and adhesion. Increases
CC       the phosphorylation levels of FAK. Interacts with and increases
CC       the mitogenic activity of HGF. Promotes synapse formation. May
CC       have a role in the perisylvian region, critical for language and
CC       cognitive development. {ECO:0000269|PubMed:16497722,
CC       ECO:0000269|PubMed:18718938, ECO:0000269|PubMed:19065654,
CC       ECO:0000269|PubMed:24179158}.
CC   -!- SUBUNIT: Forms homooligomers (By similarity). Interacts with PLAUR
CC       (via the UPAR/Ly6 domains), ADAMTS4 and CTSB. Interacts with HGF;
CC       the interaction increases the mitogenic activity of HGF.
CC       {ECO:0000250, ECO:0000269|PubMed:18718938,
CC       ECO:0000269|PubMed:22242148, ECO:0000269|PubMed:24179158}.
CC   -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cell surface. Cell
CC       junction, synapse {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in neurons of the rolandic area of
CC       the brain (at protein level). Highly expressed in the brain,
CC       placenta, lung, trachea, uterus, adrenal gland, heart, ovary and
CC       placenta. Weakly expressed in the peripheral blood, brain and bone
CC       marrow. Expressed in numerous cancer cell lines and in
CC       gastrointestinal cancer cells. Higher levels found in colorectal
CC       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 with speech dyspraxia and mental
CC       retardation X-linked (RESDX) [MIM:300643]: A condition
CC       characterized by the association of rolandic seizures with oral
CC       and speech dyspraxia, and mental retardation. Rolandic seizures
CC       occur during a period of significant brain maturation. During this
CC       time, dysfunction of neural network activities such as focal
CC       discharges may be associated with specific developmental
CC       disabilities resulting in specific cognitive impairments of
CC       language, visuo-spatial abilities or attention.
CC       {ECO:0000269|PubMed:16497722}. Note=The disease is caused by
CC       mutations 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   UniGene; Hs.306339; -.
DR   ProteinModelPortal; O60687; -.
DR   SMR; O60687; -.
DR   IntAct; O60687; 2.
DR   STRING; 9606.ENSP00000362095; -.
DR   iPTMnet; O60687; -.
DR   PhosphoSitePlus; O60687; -.
DR   BioMuta; SRPX2; -.
DR   EPD; O60687; -.
DR   jPOST; O60687; -.
DR   PaxDb; O60687; -.
DR   PeptideAtlas; O60687; -.
DR   PRIDE; O60687; -.
DR   ProteomicsDB; 49528; -.
DR   Ensembl; ENST00000373004; ENSP00000362095; ENSG00000102359.
DR   GeneID; 27286; -.
DR   KEGG; hsa:27286; -.
DR   UCSC; uc004egb.4; human.
DR   CTD; 27286; -.
DR   DisGeNET; 27286; -.
DR   EuPathDB; HostDB:ENSG00000102359.5; -.
DR   GeneCards; SRPX2; -.
DR   HGNC; HGNC:30668; SRPX2.
DR   HPA; HPA038786; -.
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   eggNOG; ENOG410IJCK; Eukaryota.
DR   eggNOG; ENOG4110JE2; LUCA.
DR   GeneTree; ENSGT00940000159149; -.
DR   HOGENOM; HOG000232093; -.
DR   HOVERGEN; HBG007217; -.
DR   InParanoid; O60687; -.
DR   KO; K19408; -.
DR   OMA; CRQIRCH; -.
DR   OrthoDB; 544541at2759; -.
DR   PhylomeDB; O60687; -.
DR   TreeFam; TF336515; -.
DR   GeneWiki; SRPX2; -.
DR   GenomeRNAi; 27286; -.
DR   PRO; PR:O60687; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   Bgee; ENSG00000102359; Expressed in 153 organ(s), highest expression level in tendon of biceps brachii.
DR   ExpressionAtlas; O60687; baseline and differential.
DR   Genevisible; O60687; HS.
DR   GO; GO:0030054; C:cell 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:0005201; F:extracellular matrix structural constituent; HDA:BHF-UCL.
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; IPR028768; SRPX2.
DR   InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR   InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR   PANTHER; PTHR19325:SF93; PTHR19325:SF93; 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; Cell junction; Complete proteome;
KW   Cytoplasm; Disease mutation; Disulfide bond; Epilepsy; Glycoprotein;
KW   Mental retardation; Polymorphism; Proteoglycan; Reference proteome;
KW   Repeat; Secreted; Signal; Sushi; Synapse.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   CHAIN        24    465       Sushi repeat-containing protein SRPX2.
FT                                /FTId=PRO_0000274525.
FT   DOMAIN       69    119       Sushi 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00302}.
FT   DOMAIN      120    178       Sushi 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00302}.
FT   DOMAIN      177    261       HYR. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00113}.
FT   DOMAIN      262    321       Sushi 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00302}.
FT   DISULFID     71    105       {ECO:0000255|PROSITE-ProRule:PRU00302}.
FT   DISULFID     91    117       {ECO:0000255|PROSITE-ProRule:PRU00302}.
FT   DISULFID    122    163       {ECO:0000255|PROSITE-ProRule:PRU00302}.
FT   DISULFID    149    176       {ECO:0000255|PROSITE-ProRule:PRU00302}.
FT   DISULFID    264    306       {ECO:0000255|PROSITE-ProRule:PRU00302}.
FT   DISULFID    292    319       {ECO:0000255|PROSITE-ProRule:PRU00302}.
FT   VARIANT      72     72       Y -> S (in RESDX; affects intracellular
FT                                processing; increases the interaction
FT                                with PLAUR; dbSNP:rs121918364).
FT                                {ECO:0000269|PubMed:16497722}.
FT                                /FTId=VAR_030312.
FT   VARIANT     287    287       T -> S (in dbSNP:rs17851822).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_030313.
FT   VARIANT     327    327       N -> S (in RESDX; unknown pathological
FT                                significance; results in a gain of
FT                                glycosylation; affects intracellular
FT                                processing; does not affect interaction
FT                                with PLAUR; dbSNP:rs121918363).
FT                                {ECO:0000269|PubMed:16497722}.
FT                                /FTId=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
//