HPLN1_HUMAN
ID HPLN1_HUMAN Reviewed; 354 AA.
AC P10915; B2R9A9;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Hyaluronan and proteoglycan link protein 1;
DE AltName: Full=Cartilage-linking protein 1;
DE Short=Cartilage-link protein;
DE AltName: Full=Proteoglycan link protein;
DE Flags: Precursor;
GN Name=HAPLN1; Synonyms=CRTL1;
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=Articular chondrocyte;
RX PubMed=2320422; DOI=10.1093/nar/18.5.1292;
RA Dudhia J., Hardingham T.E.;
RT "The primary structure of human cartilage link protein.";
RL Nucleic Acids Res. 18:1292-1292(1990).
RN [2]
RP ERRATUM OF PUBMED:2320422.
RX PubMed=2336413; DOI=10.1093/nar/18.8.2214;
RA Dudhia J., Hardingham T.E.;
RL Nucleic Acids Res. 18:2214-2214(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2286376; DOI=10.1016/0888-7543(90)90044-u;
RA Osborne-Lawrence S.L., Sinclair A.K., Hicks R.C., Lacey S.W.,
RA Eddy R.L. Jr., Byers M.G., Shows T.B., Duby A.D.;
RT "Complete amino acid sequence of human cartilage link protein (CRTL1)
RT deduced from cDNA clones and chromosomal assignment of the gene.";
RL Genomics 8:562-567(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2030970; DOI=10.1093/nar/19.8.1933;
RA Rhodes C., Savagner P., Line S., Sasaki M., Chirigos M., Doege K.,
RA Yamada Y.;
RT "Characterization of the promoter for the rat and human link protein
RT gene.";
RL Nucleic Acids Res. 19:1933-1939(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 TISSUE SPECIFICITY.
RX PubMed=11027579; DOI=10.1006/bbrc.2000.3583;
RA Hirakawa S., Oohashi T., Su W.-D., Yoshioka H., Murakami T., Arata J.,
RA Ninomiya Y.;
RT "The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and
RT characterization as a novel link protein expressed in adult brain.";
RL Biochem. Biophys. Res. Commun. 276:982-989(2000).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=12663660; DOI=10.1074/jbc.m213100200;
RA Spicer A.P., Joo A., Bowling R.A. Jr.;
RT "A hyaluronan binding link protein gene family whose members are physically
RT linked adjacent to chondroitin sulfate proteoglycan core protein genes: the
RT missing links.";
RL J. Biol. Chem. 278:21083-21091(2003).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-333.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Stabilizes the aggregates of proteoglycan monomers with
CC hyaluronic acid in the extracellular cartilage matrix.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix.
CC -!- TISSUE SPECIFICITY: Widely expressed. Weakly expressed in the brain.
CC {ECO:0000269|PubMed:11027579, ECO:0000269|PubMed:12663660}.
CC -!- SIMILARITY: Belongs to the HAPLN family. {ECO:0000305}.
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DR EMBL; X17405; CAA35462.1; -; mRNA.
DR EMBL; U43328; AAA85216.1; -; mRNA.
DR EMBL; AK313713; BAG36456.1; -; mRNA.
DR EMBL; CH471084; EAW95912.1; -; Genomic_DNA.
DR EMBL; BC057808; AAH57808.1; -; mRNA.
DR CCDS; CCDS4061.1; -.
DR PIR; S14914; LKHU.
DR RefSeq; NP_001875.1; NM_001884.3.
DR RefSeq; XP_011541470.1; XM_011543168.2.
DR RefSeq; XP_016864540.1; XM_017009051.1.
DR RefSeq; XP_016864541.1; XM_017009052.1.
DR AlphaFoldDB; P10915; -.
DR SMR; P10915; -.
DR BioGRID; 107794; 5.
DR IntAct; P10915; 2.
DR STRING; 9606.ENSP00000274341; -.
DR DrugBank; DB08818; Hyaluronic acid.
DR GlyConnect; 1380; 1 N-Linked glycan (1 site).
DR GlyGen; P10915; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P10915; -.
DR PhosphoSitePlus; P10915; -.
DR BioMuta; HAPLN1; -.
DR DMDM; 130310; -.
DR EPD; P10915; -.
DR jPOST; P10915; -.
DR MassIVE; P10915; -.
DR MaxQB; P10915; -.
DR PaxDb; P10915; -.
DR PeptideAtlas; P10915; -.
DR PRIDE; P10915; -.
DR ProteomicsDB; 52677; -.
DR Antibodypedia; 12888; 242 antibodies from 29 providers.
DR DNASU; 1404; -.
DR Ensembl; ENST00000274341.9; ENSP00000274341.4; ENSG00000145681.11.
DR GeneID; 1404; -.
DR KEGG; hsa:1404; -.
DR MANE-Select; ENST00000274341.9; ENSP00000274341.4; NM_001884.4; NP_001875.1.
DR UCSC; uc003kin.4; human.
DR CTD; 1404; -.
DR DisGeNET; 1404; -.
DR GeneCards; HAPLN1; -.
DR HGNC; HGNC:2380; HAPLN1.
DR HPA; ENSG00000145681; Tissue enriched (placenta).
DR MIM; 115435; gene.
DR neXtProt; NX_P10915; -.
DR OpenTargets; ENSG00000145681; -.
DR PharmGKB; PA26901; -.
DR VEuPathDB; HostDB:ENSG00000145681; -.
DR eggNOG; ENOG502QRAR; Eukaryota.
DR GeneTree; ENSGT00940000159267; -.
DR HOGENOM; CLU_052285_1_0_1; -.
DR InParanoid; P10915; -.
DR OMA; NYQGRVF; -.
DR OrthoDB; 743812at2759; -.
DR PhylomeDB; P10915; -.
DR TreeFam; TF332134; -.
DR PathwayCommons; P10915; -.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR SignaLink; P10915; -.
DR SIGNOR; P10915; -.
DR BioGRID-ORCS; 1404; 10 hits in 1067 CRISPR screens.
DR ChiTaRS; HAPLN1; human.
DR GeneWiki; HAPLN1; -.
DR GenomeRNAi; 1404; -.
DR Pharos; P10915; Tbio.
DR PRO; PR:P10915; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P10915; protein.
DR Bgee; ENSG00000145681; Expressed in tibia and 126 other tissues.
DR ExpressionAtlas; P10915; baseline and differential.
DR Genevisible; P10915; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0005540; F:hyaluronic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.10.100.10; -; 2.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR016187; CTDL_fold.
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; IPR013106; Ig_V-set.
DR InterPro; IPR000538; Link_dom.
DR Pfam; PF07686; V-set; 1.
DR Pfam; PF00193; Xlink; 2.
DR PRINTS; PR01265; LINKMODULE.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR SMART; SM00445; LINK; 2.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF56436; SSF56436; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS01241; LINK_1; 2.
DR PROSITE; PS50963; LINK_2; 2.
PE 2: Evidence at transcript level;
KW Disulfide bond; Extracellular matrix; Glycoprotein; Hyaluronic acid;
KW Immunoglobulin domain; Reference proteome; Repeat; Secreted.
FT PROPEP 1..15
FT /id="PRO_0000013177"
FT CHAIN 16..354
FT /note="Hyaluronan and proteoglycan link protein 1"
FT /id="PRO_0000013178"
FT DOMAIN 38..152
FT /note="Ig-like V-type"
FT DOMAIN 159..254
FT /note="Link 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DOMAIN 259..351
FT /note="Link 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..139
FT /evidence="ECO:0000250"
FT DISULFID 181..252
FT /evidence="ECO:0000250"
FT DISULFID 205..226
FT /evidence="ECO:0000250"
FT DISULFID 279..349
FT /evidence="ECO:0000250"
FT DISULFID 304..325
FT /evidence="ECO:0000250"
FT VARIANT 281
FT /note="N -> S (in dbSNP:rs6864342)"
FT /id="VAR_049316"
FT VARIANT 333
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036168"
FT CONFLICT 274
FT /note="E -> V (in Ref. 7; AAH57808)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 40166 MW; 315C96EC3AC2626A CRC64;
MKSLLLLVLI SICWADHLSD NYTLDHDRAI HIQAENGPHL LVEAEQAKVF SHRGGNVTLP
CKFYRDPTAF GSGIHKIRIK WTKLTSDYLK EVDVFVSMGY HKKTYGGYQG RVFLKGGSDS
DASLVITDLT LEDYGRYKCE VIEGLEDDTV VVALDLQGVV FPYFPRLGRY NLNFHEAQQA
CLDQDAVIAS FDQLYDAWRG GLDWCNAGWL SDGSVQYPIT KPREPCGGQN TVPGVRNYGF
WDKDKSRYDV FCFTSNFNGR FYYLIHPTKL TYDEAVQACL NDGAQIAKVG QIFAAWKILG
YDRCDAGWLA DGSVRYPISR PRRRCSPTEA AVRFVGFPDK KHKLYGVYCF RAYN
