ID   SUSD2_HUMAN             Reviewed;         822 AA.
AC   Q9UGT4; Q9H5Y6;
DT   19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 173.
DE   RecName: Full=Sushi domain-containing protein 2;
DE   Flags: Precursor;
GN   Name=SUSD2;
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=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ileal mucosa;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate;
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   [4]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-522.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [5]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-522.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [6]
RP   TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH
RP   LGALS1.
RX   PubMed=23131994; DOI=10.1158/1541-7786.mcr-12-0501-t;
RA   Watson A.P., Evans R.L., Egland K.A.;
RT   "Multiple functions of sushi domain containing 2 (SUSD2) in breast
RT   tumorigenesis.";
RL   Mol. Cancer Res. 11:74-85(2013).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP   GPR15LG.
RX   PubMed=25351403; DOI=10.1038/srep06812;
RA   Pan W., Cheng Y., Zhang H., Liu B., Mo X., Li T., Li L., Cheng X.,
RA   Zhang L., Ji J., Wang P., Han W.;
RT   "CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell
RT   growth through inducing G1 arrest.";
RL   Sci. Rep. 4:6812-6812(2014).
CC   -!- FUNCTION: May be a cytokine receptor for GPR15LG. May be a tumor
CC       suppressor; together with GPR15LG has a growth inhibitory effect on
CC       colon cancer cells which includes G1 cell cycle arrest
CC       (PubMed:25351403). May play a role in breast tumorigenesis
CC       (PubMed:23131994). {ECO:0000269|PubMed:23131994,
CC       ECO:0000269|PubMed:25351403}.
CC   -!- SUBUNIT: Interacts with LGALS1; leads to an increased amount of LGALS1
CC       on the cell surface (PubMed:23131994). Interacts with GPR15LG; the
CC       interaction is direct (PubMed:25351403). {ECO:0000269|PubMed:23131994,
CC       ECO:0000269|PubMed:25351403}.
CC   -!- INTERACTION:
CC       Q9UGT4; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-1054721, EBI-10171774;
CC       Q9UGT4; Q63HR2: TNS2; NbExp=3; IntAct=EBI-1054721, EBI-949753;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23131994,
CC       ECO:0000269|PubMed:25351403}; Single-pass type I membrane protein
CC       {ECO:0000305}. Note=SUSD2 and LGALS1 co-localized in very specific,
CC       punctate regions along the cell membrane of breast cancer cells.
CC       {ECO:0000269|PubMed:23131994}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in breast cancer, but shows a
CC       restricted expression pattern in normal tissues such as adipose,
CC       adrenal gland, kidney, lung, mammary gland, placenta, thyroid, trachea,
CC       and uterus (PubMed:23131994). Also expressed in colon; down-regulated
CC       in colon cancer tissues (PubMed:25351403).
CC       {ECO:0000269|PubMed:23131994, ECO:0000269|PubMed:25351403}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB15481.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; Z92546; CAB62953.1; -; Genomic_DNA.
DR   EMBL; AK026431; BAB15481.1; ALT_FRAME; mRNA.
DR   EMBL; BC033107; AAH33107.1; -; mRNA.
DR   CCDS; CCDS13824.1; -.
DR   RefSeq; NP_062547.1; NM_019601.3.
DR   AlphaFoldDB; Q9UGT4; -.
DR   SMR; Q9UGT4; -.
DR   BioGRID; 121109; 31.
DR   IntAct; Q9UGT4; 5.
DR   MINT; Q9UGT4; -.
DR   STRING; 9606.ENSP00000351075; -.
DR   GlyConnect; 1780; 6 N-Linked glycans (1 site).
DR   GlyCosmos; Q9UGT4; 5 sites, 8 glycans.
DR   GlyGen; Q9UGT4; 7 sites, 6 N-linked glycans (1 site), 3 O-linked glycans (3 sites).
DR   iPTMnet; Q9UGT4; -.
DR   PhosphoSitePlus; Q9UGT4; -.
DR   BioMuta; SUSD2; -.
DR   DMDM; 74735010; -.
DR   EPD; Q9UGT4; -.
DR   jPOST; Q9UGT4; -.
DR   MassIVE; Q9UGT4; -.
DR   MaxQB; Q9UGT4; -.
DR   PaxDb; 9606-ENSP00000351075; -.
DR   PeptideAtlas; Q9UGT4; -.
DR   ProteomicsDB; 84263; -.
DR   Pumba; Q9UGT4; -.
DR   Antibodypedia; 284; 353 antibodies from 23 providers.
DR   DNASU; 56241; -.
DR   Ensembl; ENST00000358321.4; ENSP00000351075.3; ENSG00000099994.11.
DR   GeneID; 56241; -.
DR   KEGG; hsa:56241; -.
DR   MANE-Select; ENST00000358321.4; ENSP00000351075.3; NM_019601.4; NP_062547.1.
DR   UCSC; uc002zzn.2; human.
DR   AGR; HGNC:30667; -.
DR   CTD; 56241; -.
DR   DisGeNET; 56241; -.
DR   GeneCards; SUSD2; -.
DR   HGNC; HGNC:30667; SUSD2.
DR   HPA; ENSG00000099994; Tissue enhanced (lung).
DR   MIM; 615825; gene.
DR   neXtProt; NX_Q9UGT4; -.
DR   OpenTargets; ENSG00000099994; -.
DR   PharmGKB; PA134942464; -.
DR   VEuPathDB; HostDB:ENSG00000099994; -.
DR   eggNOG; KOG4291; Eukaryota.
DR   GeneTree; ENSGT00730000110943; -.
DR   HOGENOM; CLU_019295_0_0_1; -.
DR   InParanoid; Q9UGT4; -.
DR   OMA; WLDHPTN; -.
DR   OrthoDB; 5405959at2759; -.
DR   PhylomeDB; Q9UGT4; -.
DR   TreeFam; TF321438; -.
DR   PathwayCommons; Q9UGT4; -.
DR   SignaLink; Q9UGT4; -.
DR   BioGRID-ORCS; 56241; 9 hits in 1147 CRISPR screens.
DR   GenomeRNAi; 56241; -.
DR   Pharos; Q9UGT4; Tbio.
DR   PRO; PR:Q9UGT4; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; Q9UGT4; Protein.
DR   Bgee; ENSG00000099994; Expressed in ileal mucosa and 133 other cell types or tissues.
DR   ExpressionAtlas; Q9UGT4; baseline and differential.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
DR   GO; GO:0051782; P:negative regulation of cell division; IDA:UniProtKB.
DR   CDD; cd00033; CCP; 1.
DR   Gene3D; 4.10.410.20; -; 1.
DR   Gene3D; 2.10.70.10; Complement Module, domain 1; 1.
DR   InterPro; IPR005533; AMOP_dom.
DR   InterPro; IPR036024; Somatomedin_B-like_dom_sf.
DR   InterPro; IPR001212; Somatomedin_B_dom.
DR   InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR   InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR   InterPro; IPR001846; VWF_type-D.
DR   PANTHER; PTHR13802; MUCIN 4-RELATED; 1.
DR   PANTHER; PTHR13802:SF63; SUSHI DOMAIN-CONTAINING PROTEIN 2; 1.
DR   Pfam; PF03782; AMOP; 1.
DR   Pfam; PF00084; Sushi; 1.
DR   Pfam; PF00094; VWD; 1.
DR   SMART; SM00723; AMOP; 1.
DR   SMART; SM00032; CCP; 1.
DR   SMART; SM00216; VWD; 1.
DR   SUPFAM; SSF57535; Complement control module/SCR domain; 1.
DR   SUPFAM; SSF90188; Somatomedin B domain; 1.
DR   PROSITE; PS50856; AMOP; 1.
DR   PROSITE; PS00524; SMB_1; 1.
DR   PROSITE; PS50958; SMB_2; 1.
DR   PROSITE; PS50923; SUSHI; 1.
DR   PROSITE; PS51233; VWFD; 1.
DR   Genevisible; Q9UGT4; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; Glycoprotein; Membrane; Receptor;
KW   Reference proteome; Signal; Sushi; Transmembrane; Transmembrane helix;
KW   Tumor suppressor.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   CHAIN           28..822
FT                   /note="Sushi domain-containing protein 2"
FT                   /id="PRO_0000249439"
FT   TOPO_DOM        28..785
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        786..806
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        807..822
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          28..66
FT                   /note="SMB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DOMAIN          285..433
FT                   /note="AMOP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00347"
FT   DOMAIN          445..639
FT                   /note="VWFD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT   DOMAIN          723..780
FT                   /note="Sushi"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   CARBOHYD        162
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        177
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        522
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952,
FT                   ECO:0000269|PubMed:19159218"
FT   DISULFID        31..44
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        31..35
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        35..62
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        42..55
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        42..44
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        48..54
FT                   /evidence="ECO:0000250|UniProtKB:Q9DBX3"
FT   DISULFID        55..62
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        725..765
FT                   /evidence="ECO:0000250"
FT   DISULFID        751..778
FT                   /evidence="ECO:0000250"
FT   VARIANT         59
FT                   /note="R -> Q (in dbSNP:rs56289213)"
FT                   /id="VAR_027416"
FT   VARIANT         110
FT                   /note="S -> T (in dbSNP:rs9680526)"
FT                   /id="VAR_027417"
FT   VARIANT         466
FT                   /note="N -> S (in dbSNP:rs8141797)"
FT                   /id="VAR_027418"
FT   CONFLICT        364
FT                   /note="Q -> R (in Ref. 2; BAB15481)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   822 AA;  90208 MW;  5B3E83862F045C90 CRC64;
     MKPALLPWAL LLLATALGPG PGPTADAQES CSMRCGALDG PCSCHPTCSG LGTCCLDFRD
     FCLEILPYSG SMMGGKDFVV RHFKMSSPTD ASVICRFKDS IQTLGHVDSS GQVHCVSPLL
     YESGRIPFTV SLDNGHSFPR AGTWLAVHPN KVSMMEKSEL VNETRWQYYG TANTSGNLSL
     TWHVKSLPTQ TITIELWGYE ETGMPYSQEW TAKWSYLYPL ATHIPNSGSF TFTPKPAPPS
     YQRWRVGALR IIDSKNYAGQ KDVQALWTND HALAWHLSDD FREDPVAWAR TQCQAWEELE
     DQLPNFLEEL PDCPCTLTQA RADSGRFFTD YGCDMEQGSV CTYHPGAVHC VRSVQASLRY
     GSGQQCCYTA DGTQLLTADS SGGSTPDRGH DWGAPPFRTP PRVPSMSHWL YDVLSFYYCC
     LWAPDCPRYM QRRPSNDCRN YRPPRLASAF GDPHFVTFDG TNFTFNGRGE YVLLEAALTD
     LRVQARAQPG TMSNGTETRG TGLTAVAVQE GNSDVVEVRL ANRTGGLEVL LNQEVLSFTE
     QSWMDLKGMF LSVAAGDRVS IMLASGAGLE VSVQGPFLSV SVLLPEKFLT HTHGLLGTLN
     NDPTDDFTLH SGRVLPPGTS PQELFLFGAN WTVHNASSLL TYDSWFLVHN FLYQPKHDPT
     FEPLFPSETT LNPSLAQEAA KLCGDDHFCN FDVAATGSLS TGTATRVAHQ LHQRRMQSLQ
     PVVSCGWLAP PPNGQKEGNR YLAGSTIYFH CDNGYSLAGA ETSTCQADGT WSSPTPKCQP
     GRSYAVLLGI IFGGLAVVAA VALVYVLLRR RKGNTHVWGA QP
//