CILP1_HUMAN
ID CILP1_HUMAN Reviewed; 1184 AA.
AC O75339; B2R8F7; Q6UW99; Q8IYI5;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Cartilage intermediate layer protein 1;
DE Short=CILP-1;
DE AltName: Full=Cartilage intermediate-layer protein;
DE Contains:
DE RecName: Full=Cartilage intermediate layer protein 1 C1;
DE Contains:
DE RecName: Full=Cartilage intermediate layer protein 1 C2;
DE Flags: Precursor;
GN Name=CILP; ORFNames=UNQ602/PRO1188;
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], PROTEIN SEQUENCE OF 39-58; 282-291; 301-317;
RP 332-338; 341-356; 361-365; 524-547; 575-594; 680-690 AND 698-707,
RP GLYCOSYLATION AT ASN-346, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY, AND
RP VARIANTS LEU-59; THR-395; GLU-575; ARG-979 AND SER-1166.
RC TISSUE=Articular cartilage;
RX PubMed=9722584; DOI=10.1074/jbc.273.36.23469;
RA Lorenzo P., Neame P., Sommarin Y., Heinegaerd D.;
RT "Cloning and deduced amino acid sequence of a novel cartilage protein
RT (CILP) identifies a proform including a nucleotide pyrophosphohydrolase.";
RL J. Biol. Chem. 273:23469-23475(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-59; PHE-327; THR-395;
RP GLU-575; VAL-895; ARG-979; ASN-1101; SER-1166 AND ALA-1168.
RX PubMed=10319588; DOI=10.1007/s100380050143;
RA Nakamura I., Okawa A., Ikegawa S., Takaoka K., Nakamura Y.;
RT "Genomic organization, mapping, and polymorphisms of the gene encoding
RT human cartilage intermediate layer protein (CILP).";
RL J. Hum. Genet. 44:203-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-59; THR-395; GLU-575;
RP ARG-979 AND SER-1166.
RX PubMed=10601732; DOI=10.1016/s0945-053x(99)00035-9;
RA Lorenzo P., Aman P., Sommarin Y., Heinegaerd D.;
RT "The human CILP gene: exon/intron organization and chromosomal mapping.";
RL Matrix Biol. 18:445-454(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-395; GLU-575 AND
RP ARG-979.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-395; GLU-575;
RP ARG-979 AND SER-1166.
RC TISSUE=Testis;
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLU-575; ARG-979 AND
RP SER-1166.
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 [8]
RP SUBUNIT, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=9722583; DOI=10.1074/jbc.273.36.23463;
RA Lorenzo P., Bayliss M.T., Heinegaerd D.;
RT "A novel cartilage protein (CILP) present in the mid-zone of human
RT articular cartilage increases with age.";
RL J. Biol. Chem. 273:23463-23468(1998).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=12483726; DOI=10.1002/art.10632;
RA Hirose J., Ryan L.M., Masuda I.;
RT "Up-regulated expression of cartilage intermediate-layer protein and ANK in
RT articular hyaline cartilage from patients with calcium pyrophosphate
RT dihydrate crystal deposition disease.";
RL Arthritis Rheum. 46:3218-3229(2002).
RN [10]
RP INVOLVEMENT IN OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS.
RX PubMed=11315923;
RX DOI=10.1002/1529-0131(200104)44:4<838::aid-anr140>3.0.co;2-c;
RA Tsuruha J., Masuko-Hongo K., Kato T., Sakata M., Nakamura H., Nishioka K.;
RT "Implication of cartilage intermediate layer protein in cartilage
RT destruction in subsets of patients with osteoarthritis and rheumatoid
RT arthritis.";
RL Arthritis Rheum. 44:838-845(2001).
RN [11]
RP FUNCTION.
RX PubMed=12746903; DOI=10.1002/art.10927;
RA Johnson K., Farley D., Hu S.-I., Terkeltaub R.;
RT "One of two chondrocyte-expressed isoforms of cartilage intermediate-layer
RT protein functions as an insulin-like growth factor 1 antagonist.";
RL Arthritis Rheum. 48:1302-1314(2003).
RN [12]
RP IMMUNIZATION.
RX PubMed=14962958; DOI=10.1136/ard.2003.008045;
RA Yao Z., Nakamura H., Masuko-Hongo K., Suzuki-Kurokawa M., Nishioka K.,
RA Kato T.;
RT "Characterisation of cartilage intermediate layer protein (CILP)-induced
RT arthropathy in mice.";
RL Ann. Rheum. Dis. 63:252-258(2004).
RN [13]
RP INVOLVEMENT IN OSTEOARTHRITIS.
RX PubMed=15378262; DOI=10.1007/s00296-004-0497-2;
RA Du H., Masuko-Hongo K., Nakamura H., Xiang Y., Bao C.-D., Wang X.-D.,
RA Chen S.-L., Nishioka K., Kato T.;
RT "The prevalence of autoantibodies against cartilage intermediate layer
RT protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients
RT with early-stage knee osteoarthritis: evidence of a variety of autoimmune
RT processes.";
RL Rheumatol. Int. 26:35-41(2005).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH TGFB1,
RP INVOLVEMENT IN IDD, AND VARIANT THR-395.
RX PubMed=15864306; DOI=10.1038/ng1557;
RA Seki S., Kawaguchi Y., Chiba K., Mikami Y., Kizawa H., Oya T., Mio F.,
RA Mori M., Miyamoto Y., Masuda I., Tsunoda T., Kamata M., Kubo T., Toyama Y.,
RA Kimura T., Nakamura Y., Ikegawa S.;
RT "A functional SNP in CILP, encoding cartilage intermediate layer protein,
RT is associated with susceptibility to lumbar disc disease.";
RL Nat. Genet. 37:607-612(2005).
RN [15]
RP VARIANTS HIS-495 AND THR-1032.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Probably plays a role in cartilage scaffolding. May act by
CC antagonizing TGF-beta1 (TGFB1) and IGF1 functions. Has the ability to
CC suppress IGF1-induced proliferation and sulfated proteoglycan
CC synthesis, and inhibits ligand-induced IGF1R autophosphorylation. May
CC inhibit TGFB1-mediated induction of cartilage matrix genes via its
CC interaction with TGFB1. Overexpression may lead to impair chondrocyte
CC growth and matrix repair and indirectly promote inorganic pyrophosphate
CC (PPi) supersaturation in aging and osteoarthritis cartilage.
CC {ECO:0000269|PubMed:12746903, ECO:0000269|PubMed:15864306}.
CC -!- SUBUNIT: Monomer. Interacts with TGFB1. {ECO:0000269|PubMed:15864306,
CC ECO:0000269|PubMed:9722583}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:15864306}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in cartilage. Localizes in
CC the intermediates layer of articular cartilage but neither in the
CC superficial nor in the deepest regions. Specifically and highly
CC expressed in intervertebral disk tissue. Expression increases with
CC aging in hip articular cartilage. Overexpressed in articular hyaline
CC cartilage from patients with calcium pyrophosphate dihydrate crystal
CC deposition disease (CPPD). Expression in intervertebral disk tissue
CC from individuals with lumbar disk disease increases as disk
CC degeneration progresses. {ECO:0000269|PubMed:12483726,
CC ECO:0000269|PubMed:15864306, ECO:0000269|PubMed:9722583,
CC ECO:0000269|PubMed:9722584}.
CC -!- PTM: Cleaved into 2 chains possibly by a furin-like protease upon or
CC preceding secretion.
CC -!- DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common
CC musculo-skeletal disorder caused by degeneration of intervertebral
CC disks of the lumbar spine. It results in low-back pain and unilateral
CC leg pain. {ECO:0000269|PubMed:15864306}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Antibodies against CILP are detected in patients with
CC early-stage knee osteoarthritis and rheumatoid arthritis.
CC -!- CAUTION: Was originally thought to constitute the ATP pyrophosphatase
CC enzyme (NTPPH). However, it was later shown (PubMed:12746903 and
CC PubMed:15864306) that it is not the case. {ECO:0000305}.
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DR EMBL; AF035408; AAC33838.1; -; mRNA.
DR EMBL; AB022430; BAA76692.1; -; Genomic_DNA.
DR EMBL; AF035455; AAF14689.1; -; Genomic_DNA.
DR EMBL; AF035448; AAF14689.1; JOINED; Genomic_DNA.
DR EMBL; AF035451; AAF14689.1; JOINED; Genomic_DNA.
DR EMBL; AF035453; AAF14689.1; JOINED; Genomic_DNA.
DR EMBL; AF035449; AAF14689.1; JOINED; Genomic_DNA.
DR EMBL; AY358904; AAQ89263.1; -; mRNA.
DR EMBL; AK313352; BAG36154.1; -; mRNA.
DR EMBL; AC068213; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035776; AAH35776.1; -; mRNA.
DR CCDS; CCDS10203.1; -.
DR PIR; T09484; T09484.
DR RefSeq; NP_003604.3; NM_003613.3.
DR AlphaFoldDB; O75339; -.
DR BioGRID; 114057; 2.
DR IntAct; O75339; 1.
DR STRING; 9606.ENSP00000261883; -.
DR GlyConnect; 1075; 15 N-Linked glycans (5 sites).
DR GlyGen; O75339; 11 sites, 13 N-linked glycans (5 sites), 2 O-linked glycans (3 sites).
DR iPTMnet; O75339; -.
DR PhosphoSitePlus; O75339; -.
DR BioMuta; CILP; -.
DR jPOST; O75339; -.
DR MassIVE; O75339; -.
DR PaxDb; O75339; -.
DR PeptideAtlas; O75339; -.
DR PRIDE; O75339; -.
DR ProteomicsDB; 49908; -.
DR Antibodypedia; 760; 157 antibodies from 30 providers.
DR DNASU; 8483; -.
DR Ensembl; ENST00000261883.6; ENSP00000261883.4; ENSG00000138615.6.
DR GeneID; 8483; -.
DR KEGG; hsa:8483; -.
DR MANE-Select; ENST00000261883.6; ENSP00000261883.4; NM_003613.4; NP_003604.4.
DR UCSC; uc002aon.3; human.
DR CTD; 8483; -.
DR DisGeNET; 8483; -.
DR GeneCards; CILP; -.
DR HGNC; HGNC:1980; CILP.
DR HPA; ENSG00000138615; Low tissue specificity.
DR MalaCards; CILP; -.
DR MIM; 603489; gene.
DR MIM; 603932; phenotype.
DR neXtProt; NX_O75339; -.
DR OpenTargets; ENSG00000138615; -.
DR PharmGKB; PA26518; -.
DR VEuPathDB; HostDB:ENSG00000138615; -.
DR eggNOG; ENOG502QQ8H; Eukaryota.
DR GeneTree; ENSGT00390000008152; -.
DR HOGENOM; CLU_008073_0_0_1; -.
DR InParanoid; O75339; -.
DR OMA; RAETPYM; -.
DR OrthoDB; 629181at2759; -.
DR PhylomeDB; O75339; -.
DR TreeFam; TF330132; -.
DR PathwayCommons; O75339; -.
DR Reactome; R-HSA-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
DR SignaLink; O75339; -.
DR BioGRID-ORCS; 8483; 15 hits in 1061 CRISPR screens.
DR ChiTaRS; CILP; human.
DR GeneWiki; CILP; -.
DR GenomeRNAi; 8483; -.
DR Pharos; O75339; Tbio.
DR PRO; PR:O75339; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; O75339; protein.
DR Bgee; ENSG00000138615; Expressed in calcaneal tendon and 155 other tissues.
DR Genevisible; O75339; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; IGI:BHF-UCL.
DR Gene3D; 2.20.100.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR008969; CarboxyPept-like_regulatory.
DR InterPro; IPR039675; CILP1/CILP2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR025155; WxxW_domain.
DR PANTHER; PTHR15031; PTHR15031; 1.
DR Pfam; PF13330; Mucin2_WxxW; 1.
DR Pfam; PF00090; TSP_1; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49464; SSF49464; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS50092; TSP1; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Extracellular matrix; Glycoprotein; Immunoglobulin domain;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1184
FT /note="Cartilage intermediate layer protein 1"
FT /id="PRO_0000014671"
FT CHAIN 22..?724
FT /note="Cartilage intermediate layer protein 1 C1"
FT /id="PRO_0000014672"
FT CHAIN ?725..1184
FT /note="Cartilage intermediate layer protein 1 C2"
FT /id="PRO_0000014673"
FT DOMAIN 149..201
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 309..395
FT /note="Ig-like C2-type"
FT REGION 1136..1170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1136..1162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:9722584"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 550
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 631
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1000
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1056
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 161..195
FT /evidence="ECO:0000250"
FT DISULFID 165..200
FT /evidence="ECO:0000250"
FT DISULFID 177..185
FT /evidence="ECO:0000250"
FT DISULFID 330..376
FT /evidence="ECO:0000250"
FT VARIANT 59
FT /note="W -> L (in dbSNP:rs2585033)"
FT /evidence="ECO:0000269|PubMed:10319588,
FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:9722584"
FT /id="VAR_022768"
FT VARIANT 327
FT /note="S -> F"
FT /evidence="ECO:0000269|PubMed:10319588"
FT /id="VAR_022769"
FT VARIANT 395
FT /note="I -> T (associated with susceptibility to lumbar
FT disk disease in Japanese; increases binding and inhibition
FT of TGFB1; dbSNP:rs2073711)"
FT /evidence="ECO:0000269|PubMed:10319588,
FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:9722584"
FT /id="VAR_022770"
FT VARIANT 495
FT /note="R -> H (in dbSNP:rs149286218)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069430"
FT VARIANT 575
FT /note="K -> E (in dbSNP:rs2679118)"
FT /evidence="ECO:0000269|PubMed:10319588,
FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9722584"
FT /id="VAR_022771"
FT VARIANT 895
FT /note="A -> V (in dbSNP:rs771628304)"
FT /evidence="ECO:0000269|PubMed:10319588"
FT /id="VAR_022772"
FT VARIANT 979
FT /note="Q -> R (in dbSNP:rs2679117)"
FT /evidence="ECO:0000269|PubMed:10319588,
FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9722584"
FT /id="VAR_022773"
FT VARIANT 1032
FT /note="S -> T (in dbSNP:rs768702821)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069431"
FT VARIANT 1101
FT /note="D -> N (in dbSNP:rs769023414)"
FT /evidence="ECO:0000269|PubMed:10319588"
FT /id="VAR_022774"
FT VARIANT 1166
FT /note="G -> S (in dbSNP:rs938952)"
FT /evidence="ECO:0000269|PubMed:10319588,
FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9722584"
FT /id="VAR_022775"
FT VARIANT 1168
FT /note="V -> A (in dbSNP:rs747702148)"
FT /evidence="ECO:0000269|PubMed:10319588"
FT /id="VAR_022776"
FT CONFLICT 54
FT /note="G -> M (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="T -> D (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="R -> D (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="D -> T (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1184 AA; 132565 MW; 190B0316404D3B84 CRC64;
MVGTKAWVFS FLVLEVTSVL GRQTMLTQSV RRVQPGKKNP SIFAKPADTL ESPGEWTTWF
NIDYPGGKGD YERLDAIRFY YGDRVCARPL RLEARTTDWT PAGSTGQVVH GSPREGFWCL
NREQRPGQNC SNYTVRFLCP PGSLRRDTER IWSPWSPWSK CSAACGQTGV QTRTRICLAE
MVSLCSEASE EGQHCMGQDC TACDLTCPMG QVNADCDACM CQDFMLHGAV SLPGGAPASG
AAIYLLTKTP KLLTQTDSDG RFRIPGLCPD GKSILKITKV KFAPIVLTMP KTSLKAATIK
AEFVRAETPY MVMNPETKAR RAGQSVSLCC KATGKPRPDK YFWYHNDTLL DPSLYKHESK
LVLRKLQQHQ AGEYFCKAQS DAGAVKSKVA QLIVIASDET PCNPVPESYL IRLPHDCFQN
ATNSFYYDVG RCPVKTCAGQ QDNGIRCRDA VQNCCGISKT EEREIQCSGY TLPTKVAKEC
SCQRCTETRS IVRGRVSAAD NGEPMRFGHV YMGNSRVSMT GYKGTFTLHV PQDTERLVLT
FVDRLQKFVN TTKVLPFNKK GSAVFHEIKM LRRKKPITLE AMETNIIPLG EVVGEDPMAE
LEIPSRSFYR QNGEPYIGKV KASVTFLDPR NISTATAAQT DLNFINDEGD TFPLRTYGMF
SVDFRDEVTS EPLNAGKVKV HLDSTQVKMP EHISTVKLWS LNPDTGLWEE EGDFKFENQR
RNKREDRTFL VGNLEIRERR LFNLDVPESR RCFVKVRAYR SERFLPSEQI QGVVISVINL
EPRTGFLSNP RAWGRFDSVI TGPNGACVPA FCDDQSPDAY SAYVLASLAG EELQAVESSP
KFNPNAIGVP QPYLNKLNYR RTDHEDPRVK KTAFQISMAK PRPNSAEESN GPIYAFENLR
ACEEAPPSAA HFRFYQIEGD RYDYNTVPFN EDDPMSWTED YLAWWPKPME FRACYIKVKI
VGPLEVNVRS RNMGGTHRQT VGKLYGIRDV RSTRDRDQPN VSAACLEFKC SGMLYDQDRV
DRTLVKVIPQ GSCRRASVNP MLHEYLVNHL PLAVNNDTSE YTMLAPLDPL GHNYGIYTVT
DQDPRTAKEI ALGRCFDGTS DGSSRIMKSN VGVALTFNCV ERQVGRQSAF QYLQSTPAQS
PAAGTVQGRV PSRRQQRASR GGQRQGGVVA SLRFPRVAQQ PLIN
