HPLN4_MOUSE
ID HPLN4_MOUSE Reviewed; 400 AA.
AC Q80WM4; Q05AB1; Q80XX2;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Hyaluronan and proteoglycan link protein 4;
DE AltName: Full=Brain link protein 2;
DE Flags: Precursor;
GN Name=Hapln4; Synonyms=Bral2, Lpr4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAP22050.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAP22050.1};
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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:AAP12625.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:AAP12625.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAP12625.1};
RA Czipri M., Nesterovitch A.B., Glant T.T.;
RT "Discoordinate expression of link proteins and skeletal tissue
RT proteoglycans (aggrecan and versican) in different organs from early
RT embryonic to adult age of mice.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Diencephalon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22121037; DOI=10.1002/cne.23009;
RA Bekku Y., Saito M., Moser M., Fuchigami M., Maehara A., Nakayama M.,
RA Kusachi S., Ninomiya Y., Oohashi T.;
RT "Bral2 is indispensable for the proper localization of brevican and the
RT structural integrity of the perineuronal net in the brainstem and
RT cerebellum.";
RL J. Comp. Neurol. 520:1721-1736(2012).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30125937; DOI=10.1111/jnc.14571;
RA Edamatsu M., Miyano R., Fujikawa A., Fujii F., Hori T., Sakaba T.,
RA Oohashi T.;
RT "Hapln4/Bral2 is a selective regulator for formation and transmission of
RT GABAergic synapses between Purkinje and deep cerebellar nuclei neurons.";
RL J. Neurochem. 147:748-763(2018).
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 (PubMed:22121037). Contributes to the
CC formation and transmission of inhibitory GABAergic synapses between
CC Purkinje cells and deep cerebellar nuclei neurons (PubMed:30125937).
CC {ECO:0000269|PubMed:22121037, ECO:0000269|PubMed:30125937}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:Q9ESM3}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in brain where it is found
CC mainly throughout the midbrain and hindbrain in a perineuronal net
CC pattern. {ECO:0000269|PubMed:14550776, ECO:0000269|PubMed:22121037}.
CC -!- DEVELOPMENTAL STAGE: Expression begins at embryonic day 20 and
CC increases thereafter. Expression continues into adulthood.
CC {ECO:0000269|PubMed:14550776}.
CC -!- DISRUPTION PHENOTYPE: In deep cerebellar nuclei (DCN) neurons of
CC knockout mice, inhibitory synaptic strengths are reduced as compared to
CC those in wild-type mice, whereas the properties of excitatory synapses
CC are unaffected (PubMed:30125937). A reduction in GABAergic pre-synaptic
CC terminals of Purkinje cells are seen in the DCN neurons
CC (PubMed:30125937). Mice show significantly attenuated perineuronal nets
CC formation in the DCN, a marked decrease of brevican (BCAN) in the
CC brainstem and cerebellum and a reduction in synapse number in the DCN
CC neurons (PubMed:22121037). {ECO:0000269|PubMed:22121037,
CC ECO:0000269|PubMed:30125937}.
CC -!- SIMILARITY: Belongs to the HAPLN family. {ECO:0000305}.
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DR EMBL; AY262758; AAP22050.1; -; mRNA.
DR EMBL; AB107882; BAC79076.1; -; mRNA.
DR EMBL; AY269789; AAP12625.1; -; mRNA.
DR EMBL; AK034300; BAC28664.1; -; mRNA.
DR EMBL; BC125339; AAI25340.1; -; mRNA.
DR EMBL; BC125341; AAI25342.1; -; mRNA.
DR CCDS; CCDS40365.1; -.
DR RefSeq; NP_808568.1; NM_177900.4.
DR AlphaFoldDB; Q80WM4; -.
DR SMR; Q80WM4; -.
DR IntAct; Q80WM4; 1.
DR MINT; Q80WM4; -.
DR STRING; 10090.ENSMUSP00000007738; -.
DR GlyConnect; 2374; 2 N-Linked glycans (1 site).
DR GlyGen; Q80WM4; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q80WM4; -.
DR PhosphoSitePlus; Q80WM4; -.
DR SwissPalm; Q80WM4; -.
DR MaxQB; Q80WM4; -.
DR PaxDb; Q80WM4; -.
DR PeptideAtlas; Q80WM4; -.
DR PRIDE; Q80WM4; -.
DR ProteomicsDB; 273272; -.
DR Antibodypedia; 28414; 194 antibodies from 28 providers.
DR DNASU; 330790; -.
DR Ensembl; ENSMUST00000007738; ENSMUSP00000007738; ENSMUSG00000007594.
DR GeneID; 330790; -.
DR KEGG; mmu:330790; -.
DR UCSC; uc009lyr.1; mouse.
DR CTD; 404037; -.
DR MGI; MGI:2679531; Hapln4.
DR VEuPathDB; HostDB:ENSMUSG00000007594; -.
DR eggNOG; ENOG502QRG1; Eukaryota.
DR GeneTree; ENSGT00940000160926; -.
DR HOGENOM; CLU_052285_1_0_1; -.
DR InParanoid; Q80WM4; -.
DR OMA; QNDGPGD; -.
DR OrthoDB; 743812at2759; -.
DR PhylomeDB; Q80WM4; -.
DR TreeFam; TF332134; -.
DR BioGRID-ORCS; 330790; 0 hits in 73 CRISPR screens.
DR PRO; PR:Q80WM4; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q80WM4; protein.
DR Bgee; ENSMUSG00000007594; Expressed in primary visual cortex and 105 other tissues.
DR Genevisible; Q80WM4; MM.
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; IDA: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; IMP: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; IMP:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IMP: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..30
FT /evidence="ECO:0000255"
FT CHAIN 31..400
FT /note="Hyaluronan and proteoglycan link protein 4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000013193"
FT DOMAIN 47..155
FT /note="Ig-like C2-type"
FT DOMAIN 164..266
FT /note="Link 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323,
FT ECO:0000305"
FT DOMAIN 271..363
FT /note="Link 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323,
FT ECO:0000305"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 69..144
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 186..264
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 210..231
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 291..361
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT DISULFID 316..337
FT /evidence="ECO:0000250|UniProtKB:P03994"
FT CONFLICT 76
FT /note="A -> D (in Ref. 1; AAP22050)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 400 AA; 42809 MW; 6656BF0714698429 CRC64;
MACAPGALGH RALWAVAWGL LLLVPVLAGA QRGRKKVVHV LEGESGSVVV QTAPGQVVSH
RGGTIVLPCR YHYEAAAHGH DGVRLKWTKV VDPLAFADVF VALGPQHRAF GPYRGRAELQ
NDGPGDASLV LRNVTLQDYG RYECEVTNEL EDDVGMVKLD LEGVVFPYHP RGGRYKMTFV
EAQRACAEQD GILASAEQLH AAWRDGLDWC NAGWLRDGSV QYPVSHAREP CGGTGSTGAG
GGTNGGVRNY GYRHNAEERY DAFCFTSNLP GRVFFLKPLR PVALAGAVRA CAARGATVAK
VGQLFAAWKL QLLDRCTAGW LADGSARYPI VNPRTRCGGP RPGVRSLGFP DASRRLFGVY
CYRAPGAPDP APGGWGWGWA GGGGWAGGSR DPAAWTPLRV
