HPLN4_HUMAN
ID HPLN4_HUMAN Reviewed; 402 AA.
AC Q86UW8; A5PKW5; Q96PW2;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Hyaluronan and proteoglycan link protein 4;
DE AltName: Full=Brain link protein 2;
DE Flags: Precursor;
GN Name=HAPLN4; Synonyms=BRAL2, KIAA1926;
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 {ECO:0000312|EMBL:AAP22048.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND 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 [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=14550776; DOI=10.1016/s1044-7431(03)00133-7;
RA Bekku Y., Su W.-D., Hirakawa S., Faessler R., Ohtsuka A., Kang J.S.,
RA Sanders J., Murakami T., Ninomiya Y., Oohashi T.;
RT "Molecular cloning of Bral2, a novel brain-specific link protein, and
RT immunohistochemical colocalization with brevican in perineuronal nets.";
RL Mol. Cell. Neurosci. 24:148-159(2003).
RN [3] {ECO:0000312|EMBL:BAB67819.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:BAB67819.1};
RX PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXI. The
RT complete sequences of 60 new cDNA clones from brain which code for large
RT proteins.";
RL DNA Res. 8:179-187(2001).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
CC -!- FUNCTION: Essential for the proper localization of brevican (BCAN),
CC mainly as a perineuronal nets (PNNs)-type deposition in the brainstem
CC and cerebellum thereby playing a key role in the formation and
CC structural organization of PNNs (By similarity). Contributes to the
CC formation and transmission of inhibitory GABAergic synapses between
CC Purkinje cells and deep cerebellar nuclei neurons (By similarity).
CC {ECO:0000250|UniProtKB:Q80WM4}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:Q9ESM3}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in brain.
CC {ECO:0000269|PubMed:12663660}.
CC -!- SIMILARITY: Belongs to the HAPLN family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB67819.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY262756; AAP22048.1; -; mRNA.
DR EMBL; AB107883; BAC79077.1; -; mRNA.
DR EMBL; AB067513; BAB67819.1; ALT_INIT; mRNA.
DR EMBL; CH471106; EAW84804.1; -; Genomic_DNA.
DR EMBL; BC142644; AAI42645.1; -; mRNA.
DR EMBL; BC142698; AAI42699.1; -; mRNA.
DR CCDS; CCDS12398.1; -.
DR RefSeq; NP_075378.1; NM_023002.2.
DR AlphaFoldDB; Q86UW8; -.
DR SMR; Q86UW8; -.
DR BioGRID; 135639; 2.
DR STRING; 9606.ENSP00000291481; -.
DR GlyGen; Q86UW8; 1 site.
DR iPTMnet; Q86UW8; -.
DR PhosphoSitePlus; Q86UW8; -.
DR BioMuta; HAPLN4; -.
DR DMDM; 47605684; -.
DR jPOST; Q86UW8; -.
DR MassIVE; Q86UW8; -.
DR MaxQB; Q86UW8; -.
DR PaxDb; Q86UW8; -.
DR PeptideAtlas; Q86UW8; -.
DR PRIDE; Q86UW8; -.
DR ProteomicsDB; 69922; -.
DR Antibodypedia; 28414; 194 antibodies from 28 providers.
DR DNASU; 404037; -.
DR Ensembl; ENST00000291481.8; ENSP00000291481.5; ENSG00000187664.9.
DR GeneID; 404037; -.
DR KEGG; hsa:404037; -.
DR MANE-Select; ENST00000291481.8; ENSP00000291481.5; NM_023002.3; NP_075378.1.
DR UCSC; uc002nmb.5; human.
DR CTD; 404037; -.
DR DisGeNET; 404037; -.
DR GeneCards; HAPLN4; -.
DR HGNC; HGNC:31357; HAPLN4.
DR HPA; ENSG00000187664; Tissue enriched (brain).
DR MIM; 619710; gene.
DR neXtProt; NX_Q86UW8; -.
DR PharmGKB; PA134886721; -.
DR VEuPathDB; HostDB:ENSG00000187664; -.
DR eggNOG; ENOG502QRG1; Eukaryota.
DR GeneTree; ENSGT00940000160926; -.
DR HOGENOM; CLU_052285_1_0_1; -.
DR InParanoid; Q86UW8; -.
DR OMA; QNDGPGD; -.
DR OrthoDB; 743812at2759; -.
DR PhylomeDB; Q86UW8; -.
DR TreeFam; TF332134; -.
DR PathwayCommons; Q86UW8; -.
DR BioGRID-ORCS; 404037; 12 hits in 1063 CRISPR screens.
DR GenomeRNAi; 404037; -.
DR Pharos; Q86UW8; Tbio.
DR PRO; PR:Q86UW8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q86UW8; protein.
DR Bgee; ENSG00000187664; Expressed in primary visual cortex and 77 other tissues.
DR Genevisible; Q86UW8; HS.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0072534; C:perineuronal net; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005540; F:hyaluronic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0150043; F:structural constituent of synapse-associated extracellular matrix; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:1904862; P:inhibitory synapse assembly; ISS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; ISS:UniProtKB.
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; IPR003598; Ig_sub2.
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; SM00408; IGc2; 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; 1.
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; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..402
FT /note="Hyaluronan and proteoglycan link protein 4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000013192"
FT DOMAIN 46..161
FT /note="Ig-like C2-type"
FT DOMAIN 163..268
FT /note="Link 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323,
FT ECO:0000305"
FT DOMAIN 273..365
FT /note="Link 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323,
FT ECO:0000305"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 68..143
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 185..266
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 209..230
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 293..363
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 318..339
FT /evidence="ECO:0000250|UniProtKB:P03994"
SQ SEQUENCE 402 AA; 42801 MW; B1B6CE2098244124 CRC64;
MVCARAALGP GALWAAAWGV LLLTAPAGAQ RGRKKVVHVL EGESGSVVVQ TAPGQVVSHR
GGTIVLPCRY HYEAAAHGHD GVRLKWTKVV DPLAFTDVFV ALGPQHRAFG SYRGRAELQG
DGPGDASLVL RNVTLQDYGR YECEVTNELE DDAGMVKLDL EGVVFPYHPR GGRYKLTFAE
AQRACAEQDG ILASAEQLHA AWRDGLDWCN AGWLRDGSVQ YPVNRPREPC GGLGGTGSAG
GGGDANGGLR NYGYRHNAEE RYDAFCFTSN LPGRVFFLKP LRPVPFSGAA RACAARGAAV
AKVGQLFAAW KLQLLDRCTA GWLADGSARY PIVNPRARCG GRRPGVRSLG FPDATRRLFG
VYCYRAPGAP DPAPGGWGWG WAGGGGWAGG ARDPAAWTPL HV
