THSD4_HUMAN
ID THSD4_HUMAN Reviewed; 1018 AA.
AC Q6ZMP0; B2RTY3; B4DR13; Q6MZI3; Q6UXZ8; Q9H8E4;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Thrombospondin type-1 domain-containing protein 4;
DE AltName: Full=A disintegrin and metalloproteinase with thrombospondin motifs-like protein 6;
DE Short=ADAMTS-like protein 6;
DE Short=ADAMTSL-6;
DE Flags: Precursor;
GN Name=THSD4; ORFNames=UNQ9334/PRO34005;
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 3).
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] (ISOFORMS 1 AND 4).
RC TISSUE=Mammary gland, and Placenta;
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].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 203-1018 (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
CC -!- FUNCTION: Promotes FBN1 matrix assembly. Attenuates TGFB signaling,
CC possibly by accelerating the sequestration of large latent complexes of
CC TGFB or active TGFB by FBN1 microfibril assembly, thereby negatively
CC regulating the expression of TGFB regulatory targets, such as POSTN (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with FBN1. May interact with TGFB1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:Q3UTY6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6ZMP0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZMP0-2; Sequence=VSP_030039, VSP_030040;
CC Name=3;
CC IsoId=Q6ZMP0-3; Sequence=VSP_030036, VSP_030037, VSP_030038,
CC VSP_030041;
CC Name=4;
CC IsoId=Q6ZMP0-4; Sequence=VSP_054877, VSP_054878;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14673.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY358143; AAQ88510.1; -; mRNA.
DR EMBL; AK023772; BAB14673.1; ALT_INIT; mRNA.
DR EMBL; AK131551; BAD18685.1; -; mRNA.
DR EMBL; AK299056; BAG61125.1; -; mRNA.
DR EMBL; AC015711; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026636; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC064799; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068181; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104943; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105132; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC140868; AAI40869.1; -; mRNA.
DR EMBL; BX641106; CAE46049.1; -; mRNA.
DR CCDS; CCDS10238.2; -. [Q6ZMP0-1]
DR CCDS; CCDS66817.1; -. [Q6ZMP0-4]
DR RefSeq; NP_001273358.1; NM_001286429.1. [Q6ZMP0-4]
DR RefSeq; NP_079093.2; NM_024817.2. [Q6ZMP0-1]
DR RefSeq; XP_006720755.1; XM_006720692.3. [Q6ZMP0-1]
DR AlphaFoldDB; Q6ZMP0; -.
DR SMR; Q6ZMP0; -.
DR BioGRID; 122963; 97.
DR IntAct; Q6ZMP0; 20.
DR STRING; 9606.ENSP00000347484; -.
DR GlyConnect; 1807; 6 N-Linked glycans (3 sites).
DR GlyGen; Q6ZMP0; 6 sites, 6 N-linked glycans (3 sites), 1 O-linked glycan (3 sites).
DR iPTMnet; Q6ZMP0; -.
DR PhosphoSitePlus; Q6ZMP0; -.
DR BioMuta; THSD4; -.
DR DMDM; 166229088; -.
DR EPD; Q6ZMP0; -.
DR jPOST; Q6ZMP0; -.
DR MassIVE; Q6ZMP0; -.
DR PaxDb; Q6ZMP0; -.
DR PeptideAtlas; Q6ZMP0; -.
DR PRIDE; Q6ZMP0; -.
DR ProteomicsDB; 4917; -.
DR ProteomicsDB; 67896; -. [Q6ZMP0-1]
DR ProteomicsDB; 67897; -. [Q6ZMP0-2]
DR ProteomicsDB; 67898; -. [Q6ZMP0-3]
DR Antibodypedia; 26512; 9 antibodies from 7 providers.
DR DNASU; 79875; -.
DR Ensembl; ENST00000261862.8; ENSP00000261862.8; ENSG00000187720.15. [Q6ZMP0-1]
DR Ensembl; ENST00000355327.7; ENSP00000347484.3; ENSG00000187720.15. [Q6ZMP0-1]
DR Ensembl; ENST00000357769.4; ENSP00000350413.4; ENSG00000187720.15. [Q6ZMP0-4]
DR GeneID; 79875; -.
DR KEGG; hsa:79875; -.
DR MANE-Select; ENST00000261862.8; ENSP00000261862.8; NM_024817.3; NP_079093.2.
DR UCSC; uc002atb.2; human. [Q6ZMP0-1]
DR CTD; 79875; -.
DR DisGeNET; 79875; -.
DR GeneCards; THSD4; -.
DR HGNC; HGNC:25835; THSD4.
DR HPA; ENSG00000187720; Tissue enhanced (cervix).
DR MIM; 614476; gene.
DR neXtProt; NX_Q6ZMP0; -.
DR OpenTargets; ENSG00000187720; -.
DR PharmGKB; PA143485631; -.
DR VEuPathDB; HostDB:ENSG00000187720; -.
DR eggNOG; KOG3538; Eukaryota.
DR eggNOG; KOG4597; Eukaryota.
DR GeneTree; ENSGT00940000156594; -.
DR HOGENOM; CLU_000660_6_0_1; -.
DR InParanoid; Q6ZMP0; -.
DR OMA; EGIFMEP; -.
DR OrthoDB; 414258at2759; -.
DR PhylomeDB; Q6ZMP0; -.
DR TreeFam; TF316874; -.
DR PathwayCommons; Q6ZMP0; -.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; Q6ZMP0; -.
DR BioGRID-ORCS; 79875; 8 hits in 1062 CRISPR screens.
DR ChiTaRS; THSD4; human.
DR GenomeRNAi; 79875; -.
DR Pharos; Q6ZMP0; Tbio.
DR PRO; PR:Q6ZMP0; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q6ZMP0; protein.
DR Bgee; ENSG00000187720; Expressed in buccal mucosa cell and 151 other tissues.
DR ExpressionAtlas; Q6ZMP0; baseline and differential.
DR Genevisible; Q6ZMP0; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0001527; C:microfibril; IEA:Ensembl.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0048251; P:elastic fiber assembly; IEA:Ensembl.
DR Gene3D; 2.20.100.10; -; 7.
DR InterPro; IPR045371; ADAMTS_CR_3.
DR InterPro; IPR010294; ADAMTS_spacer1.
DR InterPro; IPR010909; PLAC.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF19236; ADAM_CR_3; 1.
DR Pfam; PF05986; ADAM_spacer1; 1.
DR Pfam; PF08686; PLAC; 1.
DR Pfam; PF00090; TSP_1; 1.
DR SMART; SM00209; TSP1; 7.
DR SUPFAM; SSF82895; SSF82895; 7.
DR PROSITE; PS50900; PLAC; 1.
DR PROSITE; PS50092; TSP1; 6.
PE 2: Evidence at transcript level;
KW Alternative splicing; Extracellular matrix; Hydrolase; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1018
FT /note="Thrombospondin type-1 domain-containing protein 4"
FT /id="PRO_0000313583"
FT DOMAIN 53..307
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 676..737
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 739..792
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 793..851
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 852..911
FT /note="TSP type-1 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 912..968
FT /note="TSP type-1 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 971..1008
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 111..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..279
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 557..578
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..360
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_030036"
FT VAR_SEQ 1..24
FT /note="MVSHFMGSLSVLCFLLLLGFQFVC -> MFVSYLILTLLHVQTAVLARPGGE
FT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054877"
FT VAR_SEQ 25..384
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054878"
FT VAR_SEQ 361..384
FT /note="AEKVIDGTPCDQNGTAICVSGQCK -> MFVSYLILTLLHVQTAVLARPGGE
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_030037"
FT VAR_SEQ 450..579
FT /note="NYLALRSRSGRSIINGNWAIDRPGKYEGGGTMFTYKRPNEISSTAGESFLAE
FT GPTNEILDVYMIHQQPNPGVHYEYVIMGTNAISPQVPPHRRPGEPFNGQMVTEGRSQEE
FT GEQKGRNEEKEDLRGEAPE -> KKKSHLKPATRGSQFSSVKVCSVPAACKLLGTPGRA
FT RQPVPAPRELEHDKNSPHCAYLSLYLTSLAQSSWRVFSLFSYVLIYLFSKYLAFNTLFA
FT LKRMALQRDRKEKTRAWCIFIKLCGREIQILPGPV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_030038"
FT VAR_SEQ 512..523
FT /note="MIHQQPNPGVHY -> VSLDVSGLFFGF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_030039"
FT VAR_SEQ 524..1018
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_030040"
FT VAR_SEQ 580..1018
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_030041"
FT CONFLICT 104
FT /note="V -> A (in Ref. 2; BAD18685)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="P -> S (in Ref. 2; BAD18685)"
FT /evidence="ECO:0000305"
FT CONFLICT 806
FT /note="C -> S (in Ref. 2; BAB14673)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1018 AA; 112450 MW; 67D710FBA3ABAFBC CRC64;
MVSHFMGSLS VLCFLLLLGF QFVCPQPSTQ HRKVPQRMAA EGAPEDDGGG GAPGVWGAWG
PWSACSRSCS GGVMEQTRPC LPRSYRLRGG QRPGAPARAF ADHVVSAVRT SVPLHRSRDE
TPALAGTDAS RQGPTVLRGS RHPQPQGLEV TGDRRSRTRG TIGPGKYGYG KAPYILPLQT
DTAHTPQRLR RQKLSSRHSR SQGASSARHG YSSPAHQVPQ HGPLYQSDSG PRSGLQAAEA
PIYQLPLTHD QGYPAASSLF HSPETSNNHG VGTHGATQSF SQPARSTAIS CIGAYRQYKL
CNTNVCPESS RSIREVQCAS YNNKPFMGRF YEWEPFAEVK GNRKCELNCQ AMGYRFYVRQ
AEKVIDGTPC DQNGTAICVS GQCKSIGCDD YLGSDKVVDK CGVCGGDNTG CQVVSGVFKH
ALTSLGYHRV VEIPEGATKI NITEMYKSNN YLALRSRSGR SIINGNWAID RPGKYEGGGT
MFTYKRPNEI SSTAGESFLA EGPTNEILDV YMIHQQPNPG VHYEYVIMGT NAISPQVPPH
RRPGEPFNGQ MVTEGRSQEE GEQKGRNEEK EDLRGEAPEM FTSESAQTFP VRHPDRFSPH
RPDNLVPPAP QPPRRSRDHN WKQLGTTECS TTCGKGSQYP IFRCVHRSTH EEAPESYCDS
SMKPTPEEEP CNIFPCPAFW DIGEWSECSK TCGLGMQHRQ VLCRQVYANR SLTVQPYRCQ
HLEKPETTST CQLKICSEWQ IRTDWTSCSV PCGVGQRTRD VKCVSNIGDV VDDEECNMKL
RPNDIENCDM GPCAKSWFLT EWSERCSAEC GAGVRTRSVV CMTNHVSSLP LEGCGNNRPA
EATPCDNGPC TGKVEWFAGS WSQCSIECGS GTQQREVICV RKNADTFEVL DPSECSFLEK
PPSQQSCHLK PCGAKWFSTE WSMCSKSCQG GFRVREVRCL SDDMTLSNLC DPQLKPEERE
SCNPQDCVPE VDENCKDKYY NCNVVVQARL CVYNYYKTAC CASCTRVANR QTGFLGSR
