CRTAP_HUMAN
ID CRTAP_HUMAN Reviewed; 401 AA.
AC O75718; B2RBL6;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Cartilage-associated protein;
DE Flags: Precursor;
GN Name=CRTAP; Synonyms=CASP;
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].
RC TISSUE=Fetal brain;
RX PubMed=10702664; DOI=10.1159/000015463;
RA Tonachini L., Morello R., Monticone M., Skaug J., Scherer S.W.,
RA Cancedda R., Castagnola P.;
RT "cDNA cloning, characterization and chromosome mapping of the gene encoding
RT human cartilage associated protein (CRTAP).";
RL Cytogenet. Cell Genet. 87:191-194(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 MRNA], AND VARIANT ASP-137.
RC TISSUE=Kidney;
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 FUNCTION, AND INVOLVEMENT IN OI7.
RX PubMed=17055431; DOI=10.1016/j.cell.2006.08.039;
RA Morello R., Bertin T.K., Chen Y., Hicks J., Tonachini L., Monticone M.,
RA Castagnola P., Rauch F., Glorieux F.H., Vranka J., Baechinger H.P.,
RA Pace J.M., Schwarze U., Byers P.H., Weis M., Fernandes R.J., Eyre D.R.,
RA Yao Z., Boyce B.F., Lee B.;
RT "CRTAP is required for prolyl 3-hydroxylation and mutations cause recessive
RT osteogenesis imperfecta.";
RL Cell 127:291-304(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP INVOLVEMENT IN OI7.
RX PubMed=21955071; DOI=10.1111/j.1399-0004.2011.01794.x;
RA Valli M., Barnes A.M., Gallanti A., Cabral W.A., Viglio S., Weis M.A.,
RA Makareeva E., Eyre D., Leikin S., Antoniazzi F., Marini J.C., Mottes M.;
RT "Deficiency of CRTAP in non-lethal recessive osteogenesis imperfecta
RT reduces collagen deposition into matrix.";
RL Clin. Genet. 82:453-459(2012).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP VARIANT OI7 PRO-67.
RX PubMed=18566967; DOI=10.1002/humu.20799;
RA Baldridge D., Schwarze U., Morello R., Lennington J., Bertin T.K.,
RA Pace J.M., Pepin M.G., Weis M., Eyre D.R., Walsh J., Lambert D., Green A.,
RA Robinson H., Michelson M., Houge G., Lindman C., Martin J., Ward J.,
RA Lemyre E., Mitchell J.J., Krakow D., Rimoin D.L., Cohn D.H., Byers P.H.,
RA Lee B.;
RT "CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta.";
RL Hum. Mutat. 29:1435-1442(2008).
RN [9]
RP VARIANTS OI7 GLU-13 AND GLU-157.
RX PubMed=19550437; DOI=10.1038/ejhg.2009.75;
RA Van Dijk F.S., Nesbitt I.M., Nikkels P.G.J., Dalton A., Bongers E.M.H.F.,
RA van de Kamp J.M., Hilhorst-Hofstee Y., Den Hollander N.S.,
RA Lachmeijer A.M.A., Marcelis C.L., Tan-Sindhunata G.M.B., van Rijn R.R.,
RA Meijers-Heijboer H., Cobben J.M., Pals G.;
RT "CRTAP mutations in lethal and severe osteogenesis imperfecta: the
RT importance of combining biochemical and molecular genetic analysis.";
RL Eur. J. Hum. Genet. 17:1560-1569(2009).
CC -!- FUNCTION: Necessary for efficient 3-hydroxylation of fibrillar collagen
CC prolyl residues. {ECO:0000269|PubMed:17055431}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Found in articular chondrocytes. Expressed in a
CC variety of tissues.
CC -!- DISEASE: Osteogenesis imperfecta 7 (OI7) [MIM:610682]: A form of
CC osteogenesis imperfecta, a connective tissue disorder characterized by
CC low bone mass, bone fragility and susceptibility to fractures after
CC minimal trauma. Disease severity ranges from very mild forms without
CC fractures to intrauterine fractures and perinatal lethality.
CC Extraskeletal manifestations, which affect a variable number of
CC patients, are dentinogenesis imperfecta, hearing loss, and blue
CC sclerae. OI7 is an autosomal recessive, severe form. Multiple fractures
CC are present at birth and patients have short stature, short humeri and
CC femora, coxa vara, and white sclera. Dentinogenesis imperfecta is
CC absent. Death can occur in the perinatal period due to secondary
CC respiratory insufficiency. {ECO:0000269|PubMed:17055431,
CC ECO:0000269|PubMed:18566967, ECO:0000269|PubMed:19550437,
CC ECO:0000269|PubMed:21955071}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the leprecan family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Osteogenesis imperfecta variant database;
CC Note=Cartilage-associated protein (CRTAP);
CC URL="http://oi.gene.le.ac.uk/home.php?select_db=CRTAP";
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DR EMBL; AJ006470; CAA07054.1; -; mRNA.
DR EMBL; AK314719; BAG37263.1; -; mRNA.
DR EMBL; BC008745; AAH08745.1; -; mRNA.
DR CCDS; CCDS2657.1; -.
DR RefSeq; NP_006362.1; NM_006371.4.
DR AlphaFoldDB; O75718; -.
DR BioGRID; 115754; 108.
DR IntAct; O75718; 32.
DR MINT; O75718; -.
DR STRING; 9606.ENSP00000323696; -.
DR GlyConnect; 1074; 8 N-Linked glycans (2 sites).
DR GlyGen; O75718; 3 sites, 8 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR iPTMnet; O75718; -.
DR MetOSite; O75718; -.
DR PhosphoSitePlus; O75718; -.
DR SwissPalm; O75718; -.
DR BioMuta; CRTAP; -.
DR EPD; O75718; -.
DR jPOST; O75718; -.
DR MassIVE; O75718; -.
DR MaxQB; O75718; -.
DR PaxDb; O75718; -.
DR PeptideAtlas; O75718; -.
DR PRIDE; O75718; -.
DR ProteomicsDB; 50176; -.
DR Antibodypedia; 27879; 260 antibodies from 29 providers.
DR DNASU; 10491; -.
DR Ensembl; ENST00000320954.11; ENSP00000323696.5; ENSG00000170275.15.
DR GeneID; 10491; -.
DR KEGG; hsa:10491; -.
DR MANE-Select; ENST00000320954.11; ENSP00000323696.5; NM_006371.5; NP_006362.1.
DR UCSC; uc003cfl.5; human.
DR CTD; 10491; -.
DR DisGeNET; 10491; -.
DR GeneCards; CRTAP; -.
DR HGNC; HGNC:2379; CRTAP.
DR HPA; ENSG00000170275; Low tissue specificity.
DR MalaCards; CRTAP; -.
DR MIM; 605497; gene.
DR MIM; 610682; phenotype.
DR neXtProt; NX_O75718; -.
DR OpenTargets; ENSG00000170275; -.
DR Orphanet; 216804; Osteogenesis imperfecta type 2.
DR Orphanet; 216812; Osteogenesis imperfecta type 3.
DR Orphanet; 216820; Osteogenesis imperfecta type 4.
DR PharmGKB; PA26900; -.
DR VEuPathDB; HostDB:ENSG00000170275; -.
DR eggNOG; KOG4459; Eukaryota.
DR GeneTree; ENSGT00940000153814; -.
DR HOGENOM; CLU_029887_0_1_1; -.
DR InParanoid; O75718; -.
DR OMA; DPNDEVM; -.
DR OrthoDB; 607176at2759; -.
DR PhylomeDB; O75718; -.
DR TreeFam; TF320837; -.
DR PathwayCommons; O75718; -.
DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR SignaLink; O75718; -.
DR BioGRID-ORCS; 10491; 12 hits in 1082 CRISPR screens.
DR ChiTaRS; CRTAP; human.
DR GeneWiki; Cartilage_associated_protein; -.
DR GenomeRNAi; 10491; -.
DR Pharos; O75718; Tbio.
DR PRO; PR:O75718; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O75718; protein.
DR Bgee; ENSG00000170275; Expressed in tendon of biceps brachii and 205 other tissues.
DR ExpressionAtlas; O75718; baseline and differential.
DR Genevisible; O75718; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; IBA:GO_Central.
DR GO; GO:1901874; P:negative regulation of post-translational protein modification; IMP:UniProtKB.
DR GO; GO:0018400; P:peptidyl-proline hydroxylation to 3-hydroxy-L-proline; IBA:GO_Central.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR Gene3D; 1.25.40.10; -; 2.
DR InterPro; IPR033212; Crtap.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR13986:SF3; PTHR13986:SF3; 1.
PE 1: Evidence at protein level;
KW Disease variant; Dwarfism; Extracellular matrix; Glycoprotein;
KW Hydroxylation; Osteogenesis imperfecta; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..401
FT /note="Cartilage-associated protein"
FT /id="PRO_0000006319"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 13
FT /note="A -> E (in OI7; severe form; dbSNP:rs137853938)"
FT /evidence="ECO:0000269|PubMed:19550437"
FT /id="VAR_063599"
FT VARIANT 67
FT /note="L -> P (in OI7; dbSNP:rs72659358)"
FT /evidence="ECO:0000269|PubMed:18566967"
FT /id="VAR_054442"
FT VARIANT 137
FT /note="E -> D (in dbSNP:rs17850371)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032846"
FT VARIANT 157
FT /note="K -> E (in OI7; severe form; dbSNP:rs137853942)"
FT /evidence="ECO:0000269|PubMed:19550437"
FT /id="VAR_063600"
FT VARIANT 261
FT /note="L -> V (in dbSNP:rs1135127)"
FT /id="VAR_053050"
SQ SEQUENCE 401 AA; 46562 MW; 4BEED4089195456F CRC64;
MEPGRRGAAA LLALLCVACA LRAGRAQYER YSFRSFPRDE LMPLESAYRH ALDKYSGEHW
AESVGYLEIS LRLHRLLRDS EAFCHRNCSA APQPEPAAGL ASYPELRLFG GLLRRAHCLK
RCKQGLPAFR QSQPSREVLA DFQRREPYKF LQFAYFKANN LPKAIAAAHT FLLKHPDDEM
MKRNMAYYKS LPGAEDYIKD LETKSYESLF IRAVRAYNGE NWRTSITDME LALPDFFKAF
YECLAACEGS REIKDFKDFY LSIADHYVEV LECKIQCEEN LTPVIGGYPV EKFVATMYHY
LQFAYYKLND LKNAAPCAVS YLLFDQNDKV MQQNLVYYQY HRDTWGLSDE HFQPRPEAVQ
FFNVTTLQKE LYDFAKENIM DDDEGEVVEY VDDLLELEET S
