HYAS3_HUMAN
ID HYAS3_HUMAN Reviewed; 553 AA.
AC O00219; A8K5T5; Q8WTZ0; Q9NYP0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Hyaluronan synthase 3;
DE EC=2.4.1.212 {ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:25795779, ECO:0000269|PubMed:26883802};
DE AltName: Full=Hyaluronate synthase 3;
DE AltName: Full=Hyaluronic acid synthase 3;
DE Short=HA synthase 3;
GN Name=HAS3 {ECO:0000312|HGNC:HGNC:4820};
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] (ISOFORM 1).
RA Spicer A.P.;
RT "Molecular characterization of hyaluronan synthase 3.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
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] (ISOFORM 2).
RC TISSUE=Prostate;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 275-464.
RX PubMed=9083017; DOI=10.1074/jbc.272.14.8957;
RA Spicer A.P., Olson J.S., McDonald J.A.;
RT "Molecular cloning and characterization of a cDNA encoding the third
RT putative mammalian hyaluronan synthase.";
RL J. Biol. Chem. 272:8957-8961(1997).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=23303191; DOI=10.1074/jbc.m112.443879;
RA Rilla K., Oikari S., Jokela T.A., Hyttinen J.M., Kaernae R., Tammi R.H.,
RA Tammi M.I.;
RT "Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc
RT concentration than HAS2 and HAS3.";
RL J. Biol. Chem. 288:5973-5983(2013).
RN [8]
RP SUBUNIT, INTERACTION WITH HAS1 AND HAS2, SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, AND FUNCTION.
RX PubMed=25795779; DOI=10.1074/jbc.m115.640581;
RA Bart G., Vico N.O., Hassinen A., Pujol F.M., Deen A.J., Ruusala A.,
RA Tammi R.H., Squire A., Heldin P., Kellokumpu S., Tammi M.I.;
RT "Fluorescence resonance energy transfer (FRET) and proximity ligation
RT assays reveal functionally relevant homo- and heteromeric complexes among
RT hyaluronan synthases HAS1, HAS2, and HAS3.";
RL J. Biol. Chem. 290:11479-11490(2015).
RN [9]
RP SUBCELLULAR LOCATION, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND GLYCOSYLATION.
RX PubMed=26883802; DOI=10.1007/s00018-016-2158-5;
RA Deen A.J., Arasu U.T., Pasonen-Seppaenen S., Hassinen A., Takabe P.,
RA Wojciechowski S., Kaernae R., Rilla K., Kellokumpu S., Tammi R., Tammi M.,
RA Oikari S.;
RT "UDP-sugar substrates of HAS3 regulate its O-GlcNAcylation, intracellular
RT traffic, extracellular shedding and correlate with melanoma progression.";
RL Cell. Mol. Life Sci. 73:3183-3204(2016).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=30394292; DOI=10.1016/j.matbio.2018.10.004;
RA Melero-Fernandez de Mera R.M., Arasu U.T., Kaernae R., Oikari S., Rilla K.,
RA Vigetti D., Passi A., Heldin P., Tammi M.I., Deen A.J.;
RT "Effects of mutations in the post-translational modification sites on the
RT trafficking of hyaluronan synthase 2 (HAS2).";
RL Matrix Biol. 80:85-103(2019).
CC -!- FUNCTION: Catalyzes the addition of GlcNAc or GlcUA monosaccharides to
CC the nascent hyaluronan polymer. Therefore, it is essential to
CC hyaluronan synthesis a major component of most extracellular matrices
CC that has a structural role in tissues architectures and regulates cell
CC adhesion, migration and differentiation. This is one of three
CC isoenzymes responsible for cellular hyaluronan synthesis.
CC {ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:25795779,
CC ECO:0000269|PubMed:26883802}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[hyaluronan](n) + UDP-N-acetyl-alpha-D-glucosamine = H(+) + N-
CC acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP;
CC Xref=Rhea:RHEA:20465, Rhea:RHEA-COMP:12583, Rhea:RHEA-COMP:12585,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132153, ChEBI:CHEBI:132154; EC=2.4.1.212;
CC Evidence={ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:25795779,
CC ECO:0000269|PubMed:26883802};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20466;
CC Evidence={ECO:0000269|PubMed:26883802};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP-
CC alpha-D-glucuronate = [hyaluronan](n+1) + H(+) + UDP;
CC Xref=Rhea:RHEA:12528, Rhea:RHEA-COMP:12585, Rhea:RHEA-COMP:12587,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132153, ChEBI:CHEBI:132154; EC=2.4.1.212;
CC Evidence={ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:25795779,
CC ECO:0000269|PubMed:26883802};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12529;
CC Evidence={ECO:0000269|PubMed:26883802};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: The enzymatic activity depends on the availability
CC of cytosolic levels of UDP-GlcUA and UDP-GlcNAc.
CC {ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:26883802}.
CC -!- PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis.
CC {ECO:0000269|PubMed:23303191}.
CC -!- SUBUNIT: Homodimers (PubMed:25795779). Forms heterodimers with HAS2 and
CC HAS1 (PubMed:25795779). {ECO:0000269|PubMed:25795779}.
CC -!- INTERACTION:
CC O00219; Q92839: HAS1; NbExp=9; IntAct=EBI-16628799, EBI-1052423;
CC O00219; Q92819: HAS2; NbExp=10; IntAct=EBI-16628799, EBI-16628852;
CC O00219; O00219: HAS3; NbExp=10; IntAct=EBI-16628799, EBI-16628799;
CC O00219-2; O95236-2: APOL3; NbExp=3; IntAct=EBI-17186025, EBI-11976321;
CC O00219-2; Q96FZ5: CMTM7; NbExp=3; IntAct=EBI-17186025, EBI-2807956;
CC O00219-2; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-17186025, EBI-2820517;
CC O00219-2; Q8N912: NRAC; NbExp=3; IntAct=EBI-17186025, EBI-12051377;
CC O00219-2; P60201-2: PLP1; NbExp=3; IntAct=EBI-17186025, EBI-12188331;
CC O00219-2; O43759-2: SYNGR1; NbExp=3; IntAct=EBI-17186025, EBI-12187159;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25795779,
CC ECO:0000269|PubMed:26883802, ECO:0000269|PubMed:30394292}; Multi-pass
CC membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:25795779}; Multi-pass membrane protein. Golgi
CC apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:O08650};
CC Multi-pass membrane protein {ECO:0000255}. Early endosome
CC {ECO:0000269|PubMed:26883802}. Note=Travels from endoplasmic reticulum
CC (ER), Golgi to plasma membrane (PubMed:26883802). Actives only when
CC present in plasma membrane (By similarity). O-GlcNAcylation controls
CC its membrane localization (PubMed:26883802). A rapid recycling of HAS3
CC between plasma membrane and endosomes is controlled by the cytosolic
CC levels of UDP-GlcUA and UDP-GlcNAc (PubMed:26883802).
CC {ECO:0000250|UniProtKB:O08650, ECO:0000269|PubMed:26883802}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00219-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00219-2; Sequence=VSP_042022;
CC -!- PTM: O-GlcNAcylation increases the hyaluronan synthase activity, HAS3
CC stability and its plasma membrane residence. The concentration of UDP-
CC GlcNAc controls the level of O-GlcNAc modification.
CC {ECO:0000269|PubMed:26883802}.
CC -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
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DR EMBL; AF232772; AAF36984.1; -; mRNA.
DR EMBL; AK291400; BAF84089.1; -; mRNA.
DR EMBL; AC009027; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83247.1; -; Genomic_DNA.
DR EMBL; CH471092; EAW83248.1; -; Genomic_DNA.
DR EMBL; BC021853; AAH21853.1; -; mRNA.
DR EMBL; U86409; AAC51209.1; -; Genomic_DNA.
DR CCDS; CCDS10870.1; -. [O00219-2]
DR CCDS; CCDS10871.1; -. [O00219-1]
DR RefSeq; NP_001186209.1; NM_001199280.1. [O00219-1]
DR RefSeq; NP_005320.2; NM_005329.2. [O00219-1]
DR RefSeq; NP_619515.1; NM_138612.2. [O00219-2]
DR RefSeq; XP_005255978.1; XM_005255921.2. [O00219-1]
DR RefSeq; XP_011521363.1; XM_011523061.2. [O00219-1]
DR AlphaFoldDB; O00219; -.
DR BioGRID; 109288; 14.
DR CORUM; O00219; -.
DR IntAct; O00219; 9.
DR STRING; 9606.ENSP00000304440; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR GlyGen; O00219; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O00219; -.
DR PhosphoSitePlus; O00219; -.
DR BioMuta; HAS3; -.
DR EPD; O00219; -.
DR MassIVE; O00219; -.
DR MaxQB; O00219; -.
DR PaxDb; O00219; -.
DR PeptideAtlas; O00219; -.
DR PRIDE; O00219; -.
DR ProteomicsDB; 47788; -. [O00219-1]
DR ProteomicsDB; 47789; -. [O00219-2]
DR Antibodypedia; 29818; 267 antibodies from 32 providers.
DR DNASU; 3038; -.
DR Ensembl; ENST00000219322.7; ENSP00000219322.3; ENSG00000103044.11. [O00219-2]
DR Ensembl; ENST00000306560.1; ENSP00000304440.1; ENSG00000103044.11. [O00219-1]
DR Ensembl; ENST00000569188.6; ENSP00000454731.1; ENSG00000103044.11. [O00219-1]
DR GeneID; 3038; -.
DR KEGG; hsa:3038; -.
DR MANE-Select; ENST00000569188.6; ENSP00000454731.1; NM_001199280.2; NP_001186209.1.
DR UCSC; uc002ewk.4; human. [O00219-1]
DR CTD; 3038; -.
DR DisGeNET; 3038; -.
DR GeneCards; HAS3; -.
DR HGNC; HGNC:4820; HAS3.
DR HPA; ENSG00000103044; Tissue enhanced (esophagus, urinary bladder).
DR MIM; 602428; gene.
DR neXtProt; NX_O00219; -.
DR OpenTargets; ENSG00000103044; -.
DR PharmGKB; PA29196; -.
DR VEuPathDB; HostDB:ENSG00000103044; -.
DR eggNOG; KOG2571; Eukaryota.
DR GeneTree; ENSGT00390000010337; -.
DR HOGENOM; CLU_029695_3_0_1; -.
DR InParanoid; O00219; -.
DR OMA; DVIVPCF; -.
DR PhylomeDB; O00219; -.
DR TreeFam; TF332506; -.
DR BRENDA; 2.4.1.212; 2681.
DR PathwayCommons; O00219; -.
DR Reactome; R-HSA-2142850; Hyaluronan biosynthesis and export.
DR SignaLink; O00219; -.
DR UniPathway; UPA00341; -.
DR BioGRID-ORCS; 3038; 17 hits in 1069 CRISPR screens.
DR ChiTaRS; HAS3; human.
DR GeneWiki; HAS3; -.
DR GenomeRNAi; 3038; -.
DR Pharos; O00219; Tbio.
DR PRO; PR:O00219; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O00219; protein.
DR Bgee; ENSG00000103044; Expressed in secondary oocyte and 140 other tissues.
DR ExpressionAtlas; O00219; baseline and differential.
DR Genevisible; O00219; HS.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0036117; C:hyaluranon cable; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050501; F:hyaluronan synthase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0085029; P:extracellular matrix assembly; ISS:UniProtKB.
DR GO; GO:0045226; P:extracellular polysaccharide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; IDA:UniProtKB.
DR GO; GO:1900106; P:positive regulation of hyaluranon cable assembly; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Endosome; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Membrane; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..553
FT /note="Hyaluronan synthase 3"
FT /id="PRO_0000197178"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..44
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..408
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 430..440
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..461
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..473
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 474..494
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 495..515
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 516..536
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 537..553
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT CARBOHYD 462
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 247..553
FT /note="ILNKYDSWISFLSSVRYWMAFNVERACQSYFGCVQCISGPLGMYRNSLLQQF
FT LEDWYHQKFLGSKCSFGDDRHLTNRVLSLGYRTKYTARSKCLTETPTKYLRWLNQQTRW
FT SKSYFREWLYNSLWFHKHHLWMTYESVVTGFFPFFLIATVIQLFYRGRIWNILLFLLTV
FT QLVGIIKATYACFLRGNAEMIFMSLYSLLYMSSLLPAKIFAIATINKSGWGTSGRKTIV
FT VNFIGLIPVSIWVAVLLGGLAYTAYCQDLFSETELAFLVSGAILYGCYWVALLMLYLAI
FT IARRCGKKPEQYSLAFAEV -> PPGKGMAVEDDQVQAAQVRATEAWSVHQRHVSREQ
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042022"
FT VARIANT 173
FT /note="R -> H (in dbSNP:rs2232229)"
FT /id="VAR_049317"
FT CONFLICT 493
FT /note="G -> E (in Ref. 1; AAF36984)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 62998 MW; 82F3B0C932EE9EA3 CRC64;
MPVQLTTALR VVGTSLFALA VLGGILAAYV TGYQFIHTEK HYLSFGLYGA ILGLHLLIQS
LFAFLEHRRM RRAGQALKLP SPRRGSVALC IAAYQEDPDY LRKCLRSAQR ISFPDLKVVM
VVDGNRQEDA YMLDIFHEVL GGTEQAGFFV WRSNFHEAGE GETEASLQEG MDRVRDVVRA
STFSCIMQKW GGKREVMYTA FKALGDSVDY IQVCDSDTVL DPACTIEMLR VLEEDPQVGG
VGGDVQILNK YDSWISFLSS VRYWMAFNVE RACQSYFGCV QCISGPLGMY RNSLLQQFLE
DWYHQKFLGS KCSFGDDRHL TNRVLSLGYR TKYTARSKCL TETPTKYLRW LNQQTRWSKS
YFREWLYNSL WFHKHHLWMT YESVVTGFFP FFLIATVIQL FYRGRIWNIL LFLLTVQLVG
IIKATYACFL RGNAEMIFMS LYSLLYMSSL LPAKIFAIAT INKSGWGTSG RKTIVVNFIG
LIPVSIWVAV LLGGLAYTAY CQDLFSETEL AFLVSGAILY GCYWVALLML YLAIIARRCG
KKPEQYSLAF AEV
