SUSD4_HUMAN
ID SUSD4_HUMAN Reviewed; 490 AA.
AC Q5VX71; D3DTB9; Q6UX62; Q9BSR0; Q9NWG0;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Sushi domain-containing protein 4;
DE Flags: Precursor;
GN Name=SUSD4; ORFNames=UNQ196/PRO222;
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 MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Embryo;
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 GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Ovary;
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 TISSUE SPECIFICITY, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23482636; DOI=10.1096/fj.12-222042;
RA Holmquist E., Okroj M., Nodin B., Jirstrom K., Blom A.M.;
RT "Sushi domain-containing protein 4 (SUSD4) inhibits complement by
RT disrupting the formation of the classical C3 convertase.";
RL FASEB J. 27:2355-2366(2013).
CC -!- FUNCTION: Acts as complement inhibitor by disrupting the formation of
CC the classical C3 convertase. Isoform 3 inhibits the classical
CC complement pathway, while membrane-bound isoform 1 inhibits deposition
CC of C3b via both the classical and alternative complement pathways.
CC {ECO:0000269|PubMed:23482636}.
CC -!- INTERACTION:
CC Q5VX71-3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12017810, EBI-16439278;
CC Q5VX71-3; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12017810, EBI-947187;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000305}; Single-pass
CC type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted
CC {ECO:0000305|PubMed:23482636}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=SUSD4a {ECO:0000303|PubMed:23482636};
CC IsoId=Q5VX71-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5VX71-2; Sequence=VSP_020840, VSP_020843;
CC Name=3; Synonyms=SUSD4b {ECO:0000303|PubMed:23482636};
CC IsoId=Q5VX71-3; Sequence=VSP_020841, VSP_020842;
CC Name=4;
CC IsoId=Q5VX71-4; Sequence=VSP_020838, VSP_020839;
CC -!- TISSUE SPECIFICITY: Isoform 3 is the predominant isoform in all tissues
CC except cortex, cerebellum, kidney, and breast. Isoform 1 is found
CC primarily in the esophagus and the brain.
CC {ECO:0000269|PubMed:23482636}.
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DR EMBL; AY358495; AAQ88859.1; -; mRNA.
DR EMBL; AK000914; BAA91421.1; -; mRNA.
DR EMBL; AL359733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359979; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93260.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93261.1; -; Genomic_DNA.
DR EMBL; BC004888; AAH04888.1; -; mRNA.
DR CCDS; CCDS31034.1; -. [Q5VX71-3]
DR CCDS; CCDS41471.1; -. [Q5VX71-1]
DR RefSeq; NP_001032252.1; NM_001037175.2. [Q5VX71-3]
DR RefSeq; NP_060452.3; NM_017982.3. [Q5VX71-1]
DR RefSeq; XP_016857076.1; XM_017001587.1. [Q5VX71-1]
DR RefSeq; XP_016857077.1; XM_017001588.1. [Q5VX71-1]
DR AlphaFoldDB; Q5VX71; -.
DR SMR; Q5VX71; -.
DR BioGRID; 120379; 48.
DR IntAct; Q5VX71; 36.
DR MINT; Q5VX71; -.
DR STRING; 9606.ENSP00000344219; -.
DR GlyGen; Q5VX71; 3 sites.
DR iPTMnet; Q5VX71; -.
DR PhosphoSitePlus; Q5VX71; -.
DR BioMuta; SUSD4; -.
DR DMDM; 74747494; -.
DR jPOST; Q5VX71; -.
DR MassIVE; Q5VX71; -.
DR PaxDb; Q5VX71; -.
DR PeptideAtlas; Q5VX71; -.
DR PRIDE; Q5VX71; -.
DR ProteomicsDB; 65576; -. [Q5VX71-1]
DR ProteomicsDB; 65577; -. [Q5VX71-2]
DR Antibodypedia; 34634; 80 antibodies from 16 providers.
DR DNASU; 55061; -.
DR Ensembl; ENST00000343846.7; ENSP00000344219.3; ENSG00000143502.16. [Q5VX71-1]
DR Ensembl; ENST00000344029.6; ENSP00000339926.6; ENSG00000143502.16. [Q5VX71-3]
DR Ensembl; ENST00000366878.9; ENSP00000355843.4; ENSG00000143502.16. [Q5VX71-1]
DR Ensembl; ENST00000681305.1; ENSP00000505262.1; ENSG00000143502.16. [Q5VX71-1]
DR Ensembl; ENST00000681669.1; ENSP00000505495.1; ENSG00000143502.16. [Q5VX71-1]
DR GeneID; 55061; -.
DR KEGG; hsa:55061; -.
DR MANE-Select; ENST00000366878.9; ENSP00000355843.4; NM_017982.4; NP_060452.3.
DR UCSC; uc001hnx.3; human. [Q5VX71-1]
DR CTD; 55061; -.
DR DisGeNET; 55061; -.
DR GeneCards; SUSD4; -.
DR HGNC; HGNC:25470; SUSD4.
DR HPA; ENSG00000143502; Tissue enhanced (brain, esophagus).
DR MIM; 615827; gene.
DR neXtProt; NX_Q5VX71; -.
DR OpenTargets; ENSG00000143502; -.
DR PharmGKB; PA142670855; -.
DR VEuPathDB; HostDB:ENSG00000143502; -.
DR eggNOG; ENOG502QU1F; Eukaryota.
DR GeneTree; ENSGT00940000160410; -.
DR HOGENOM; CLU_077058_0_0_1; -.
DR InParanoid; Q5VX71; -.
DR OMA; IIACHEG; -.
DR OrthoDB; 560016at2759; -.
DR PhylomeDB; Q5VX71; -.
DR TreeFam; TF332459; -.
DR PathwayCommons; Q5VX71; -.
DR SignaLink; Q5VX71; -.
DR BioGRID-ORCS; 55061; 9 hits in 1063 CRISPR screens.
DR ChiTaRS; SUSD4; human.
DR GenomeRNAi; 55061; -.
DR Pharos; Q5VX71; Tbio.
DR PRO; PR:Q5VX71; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5VX71; protein.
DR Bgee; ENSG00000143502; Expressed in lower esophagus mucosa and 169 other tissues.
DR ExpressionAtlas; Q5VX71; baseline and differential.
DR Genevisible; Q5VX71; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045957; P:negative regulation of complement activation, alternative pathway; IDA:UniProtKB.
DR GO; GO:0045959; P:negative regulation of complement activation, classical pathway; IDA:UniProtKB.
DR GO; GO:0030449; P:regulation of complement activation; IDA:UniProtKB.
DR CDD; cd00033; CCP; 4.
DR InterPro; IPR042985; SUSD4.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR PANTHER; PTHR47007; PTHR47007; 1.
DR Pfam; PF00084; Sushi; 4.
DR SMART; SM00032; CCP; 4.
DR SUPFAM; SSF57535; SSF57535; 4.
DR PROSITE; PS50923; SUSHI; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Complement pathway; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Membrane; Reference proteome; Repeat; Secreted;
KW Signal; Sushi; Transmembrane; Transmembrane helix.
FT SIGNAL 1..41
FT /evidence="ECO:0000255"
FT CHAIN 42..490
FT /note="Sushi domain-containing protein 4"
FT /id="PRO_0000251975"
FT TOPO_DOM 42..319
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 341..490
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 55..119
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 120..179
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 178..239
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 241..304
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..472
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 57..99
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 85..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 122..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 147..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 180..224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 210..237
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 243..289
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 274..302
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 186..236
FT /note="SSNGYVNISELQTSFPVGTVISYRCFPGFKLDGSAYLECLQNLIWSSSPPR
FT -> PQHTPAQGTRTQAQGSQKPVTASQALLSCSKVCIHLPGAKRAPTLLRTTLT (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020838"
FT VAR_SEQ 237..490
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020839"
FT VAR_SEQ 241
FT /note="E -> EAQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_020840"
FT VAR_SEQ 242..290
FT /note="VCPLPPMVSHGDFVCHPRPCERYNHGTVVEFYCDPGYSLTSDYKYITCQ ->
FT GGRPEHLFPVLYFPHIRLAAAVLYFCPVLKSSPTPAPTCSSTSTTTSLF (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020841"
FT VAR_SEQ 291..490
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020842"
FT VAR_SEQ 478..490
FT /note="DIADEIPLMEEDP -> HHAHWVLFLRN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_020843"
SQ SEQUENCE 490 AA; 53778 MW; 15392C2774BEFF22 CRC64;
MYHGMNPSNG DGFLEQQQQQ QQPQSPQRLL AVILWFQLAL CFGPAQLTGG FDDLQVCADP
GIPENGFRTP SGGVFFEGSV ARFHCQDGFK LKGATKRLCL KHFNGTLGWI PSDNSICVQE
DCRIPQIEDA EIHNKTYRHG EKLIITCHEG FKIRYPDLHN MVSLCRDDGT WNNLPICQGC
LRPLASSNGY VNISELQTSF PVGTVISYRC FPGFKLDGSA YLECLQNLIW SSSPPRCLAL
EVCPLPPMVS HGDFVCHPRP CERYNHGTVV EFYCDPGYSL TSDYKYITCQ YGEWFPSYQV
YCIKSEQTWP STHETLLTTW KIVAFTATSV LLVLLLVILA RMFQTKFKAH FPPRGPPRSS
SSDPDFVVVD GVPVMLPSYD EAVSGGLSAL GPGYMASVGQ GCPLPVDDQS PPAYPGSGDT
DTGPGESETC DSVSGSSELL QSLYSPPRCQ ESTHPASDNP DIIASTAEEV ASTSPGIDIA
DEIPLMEEDP
