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   27-MAR-2024, entry version 178.
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; Note=The
CC       CRTAP gene homepage;
CC       URL="https://www.LOVD.nl/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; 120.
DR   IntAct; O75718; 34.
DR   MINT; O75718; -.
DR   STRING; 9606.ENSP00000323696; -.
DR   GlyConnect; 1074; 8 N-Linked glycans (2 sites).
DR   GlyCosmos; O75718; 3 sites, 9 glycans.
DR   GlyGen; O75718; 5 sites, 8 N-linked glycans (2 sites), 1 O-linked glycan (3 sites).
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; 9606-ENSP00000323696; -.
DR   PeptideAtlas; O75718; -.
DR   ProteomicsDB; 50176; -.
DR   Pumba; O75718; -.
DR   Antibodypedia; 27879; 276 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   AGR; HGNC:2379; -.
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; 2050; Cole-Carpenter syndrome.
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; WPETVEY; -.
DR   OrthoDB; 5398065at2759; -.
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 1162 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 207 other cell types or tissues.
DR   ExpressionAtlas; O75718; baseline and differential.
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:0050821; P:protein stabilization; IMP:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 2.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   PANTHER; PTHR13986:SF3; CARTILAGE-ASSOCIATED PROTEIN; 1.
DR   PANTHER; PTHR13986; PROTEIN LYSINE HYDROXYLATION COMPLEX COMPONENT; 1.
DR   Genevisible; O75718; HS.
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
//