ID   HYAS2_MOUSE             Reviewed;         552 AA.
AC   P70312; P70411; Q62405; Q68EF7;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 4.
DT   24-JAN-2024, entry version 160.
DE   RecName: Full=Hyaluronan synthase 2;
DE            EC=2.4.1.212 {ECO:0000269|PubMed:10455188};
DE   AltName: Full=Hyaluronate synthase 2;
DE   AltName: Full=Hyaluronic acid synthase 2;
DE            Short=HA synthase 2;
GN   Name=Has2 {ECO:0000312|MGI:MGI:107821};
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J;
RX   PubMed=8798545; DOI=10.1074/jbc.271.38.23400;
RA   Spicer A.P., Augustine M.L., McDonald J.A.;
RT   "Molecular cloning and characterization of a putative mouse hyaluronan
RT   synthase.";
RL   J. Biol. Chem. 271:23400-23406(1996).
RN   [2]
RP   SEQUENCE REVISION TO 138.
RA   Spicer A.P., Augustine M.L., McDonald J.A.;
RL   Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=CD-1;
RX   PubMed=9016821; DOI=10.1006/abbi.1996.9793;
RA   Fueloep C., Salustri A., Hascall V.C.;
RT   "Coding sequence of a hyaluronan synthase homologue expressed during
RT   expansion of the mouse cumulus-oocyte complex.";
RL   Arch. Biochem. Biophys. 337:261-266(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Thymus;
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 GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; 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   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 215-348.
RC   STRAIN=Swiss Webster; TISSUE=Embryo;
RX   PubMed=8643441; DOI=10.1073/pnas.93.10.4548;
RA   Semino C.E., Specht C.A., Raimondi A., Robbins P.W.;
RT   "Homologs of the Xenopus developmental gene DG42 are present in zebrafish
RT   and mouse and are involved in the synthesis of Nod-like chitin
RT   oligosaccharides during early embryogenesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:4548-4553(1996).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=10455188; DOI=10.1074/jbc.274.35.25085;
RA   Itano N., Sawai T., Yoshida M., Lenas P., Yamada Y., Imagawa M.,
RA   Shinomura T., Hamaguchi M., Yoshida Y., Ohnuki Y., Miyauchi S.,
RA   Spicer A.P., McDonald J.A., Kimata K.;
RT   "Three isoforms of mammalian hyaluronan synthases have distinct enzymatic
RT   properties.";
RL   J. Biol. Chem. 274:25085-25092(1999).
RN   [9]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX   PubMed=10930438; DOI=10.1172/jci10272;
RA   Camenisch T.D., Spicer A.P., Brehm-Gibson T., Biesterfeldt J.,
RA   Augustine M.L., Calabro A. Jr., Kubalak S., Klewer S.E., McDonald J.A.;
RT   "Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis
RT   and hyaluronan-mediated transformation of epithelium to mesenchyme.";
RL   J. Clin. Invest. 106:349-360(2000).
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 the isozymes
CC       catalyzing that reaction and it is particularly responsible for the
CC       synthesis of high molecular mass hyaluronan (PubMed:10455188). Required
CC       for the transition of endocardial cushion cells into mesenchymal cells,
CC       a process crucial for heart development (PubMed:10930438). May also
CC       play a role in vasculogenesis. High molecular mass hyaluronan also play
CC       a role in early contact inhibition a process which stops cell growth
CC       when cells come into contact with each other or the extracellular
CC       matrix. {ECO:0000269|PubMed:10455188, ECO:0000269|PubMed:10930438}.
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 (By similarity). This is one of
CC       three isoenzymes responsible for cellular hyaluronan synthesis and it
CC       is particularly responsible for the synthesis of high molecular mass
CC       hyaluronan (PubMed:10455188). {ECO:0000250|UniProtKB:Q92819,
CC       ECO:0000269|PubMed:10455188}.
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:10455188};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20466;
CC         Evidence={ECO:0000305|PubMed:10455188};
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:10455188};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12529;
CC         Evidence={ECO:0000305|PubMed:10455188};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.2 mM for UDP-Glc-NAc (at pH 7.1 and 37 degrees Celsius, in the
CC         presence of 15 mM MgCl2) {ECO:0000269|PubMed:10455188};
CC         KM=0.3 mM for UDP-Glc-UA (at pH 7.1 and 37 degrees Celsius, in the
CC         presence of 15 mM MgCl2) {ECO:0000269|PubMed:10455188};
CC   -!- PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis.
CC       {ECO:0000269|PubMed:10455188}.
CC   -!- SUBUNIT: Homodimer; dimerization promotes enzymatic activity. Forms
CC       heterodimer with HAS3. Forms heterodimer with HAS1.
CC       {ECO:0000250|UniProtKB:Q92819}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q92819};
CC       Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum
CC       membrane {ECO:0000250|UniProtKB:Q92819}; Multi-pass membrane protein
CC       {ECO:0000255}. Vesicle {ECO:0000250|UniProtKB:Q92819}. Golgi apparatus
CC       membrane {ECO:0000250|UniProtKB:Q92819}; Multi-pass membrane protein
CC       {ECO:0000255}. Lysosome {ECO:0000250|UniProtKB:Q92819}. Note=Travels
CC       from endoplasmic reticulum (ER), Golgi to plasma membrane and either
CC       back to endosomes and lysosomes, or out into extracellular vesicles.
CC       Post-translational modifications control HAS2 trafficking.
CC       {ECO:0000250|UniProtKB:Q92819}.
CC   -!- TISSUE SPECIFICITY: Expressed in heart, brain, spleen, lung and
CC       skeletal muscle. {ECO:0000269|PubMed:8798545}.
CC   -!- DEVELOPMENTAL STAGE: Detected from 7.5 dpc through birth. At 8.5 dpc,
CC       predominantly expressed in the epithelium of the foregut diverticulum,
CC       the cephalic mesenchyme, the allantois, and in the myocardium and
CC       endocardium of the heart. At 9.5 dpc, prominent expression is detected
CC       in cephalic, foregut and periaortic mesenchymes, the septum transversum
CC       and the cardiovascular system. Also present in the atrial and
CC       ventricular endothelium and the myocardium of the atrioventricular
CC       canal region. By 10.5 dpc, highly expressed in endothelial cells in the
CC       atrioventricular canal and outflow tract that transform into
CC       mesenchymal cells and invade the underlying matrix. Later, expressed by
CC       mesenchymal cells during elevation of the secondary palate and by
CC       hypertrophic chondrocytes within epiphysial growth plates.
CC       {ECO:0000269|PubMed:10930438}.
CC   -!- PTM: Phosphorylation at Thr-328 is essential for hyaluronan synthase
CC       activity. {ECO:0000250|UniProtKB:Q92819}.
CC   -!- PTM: O-GlcNAcylation at Ser-221 increases the stability of HAS2 and
CC       plasma membrane localization. {ECO:0000250|UniProtKB:Q92819}.
CC   -!- PTM: Ubiquitination at Lys-190; this ubiquitination is essential for
CC       hyaluronan synthase activity and homo- or hetero-oligomerization. Can
CC       also be poly-ubiquitinated. Deubiquitinated by USP17L22/USP17 and USP4.
CC       USP17L22/USP17 efficiently removes 'Lys-63'- and 'Lys-48'-linked
CC       polyubiquitin chains, whereas USP4 preferentially removes
CC       monoubiquitination and, partially, both 'Lys-63'- and 'Lys-48'-linked
CC       polyubiquitin chain. {ECO:0000250|UniProtKB:Q92819}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethal. At day 9.5 dpc, the
CC       distribution of homozygous embryos approaches Mendelian frequency while
CC       only occasional viable embryos were found at 10.5 dpc. Embryos
CC       exhibited growth retardation, scant numbers of red blood cells, and
CC       lacked vitelline vessels in the yolk sac. The visceral endoderm and
CC       mesoderm forming the yolk sac was not fused except at discrete foci.
CC       The heart was thinwalled and relatively bloodless, and often exhibited
CC       marked pericardial swelling. The heart lacks cardiac jelly, endocardial
CC       cushions and trabeculae. A marked reduction in vessels in homozygous
CC       embryos is also observed. Somites were present but distorted. Some of
CC       the 9.5 dpc embryos had failed to turn, and exhibited posterior defects
CC       as well as cephalic mesenchyme abnormalities.
CC       {ECO:0000269|PubMed:10930438}.
CC   -!- SIMILARITY: Belongs to the NodC/HAS family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=an unexpected turn of events
CC       - Issue 155 of December 2013;
CC       URL="https://web.expasy.org/spotlight/back_issues/155/";
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DR   EMBL; U52524; AAC53309.2; -; mRNA.
DR   EMBL; U69695; AAB17609.1; -; mRNA.
DR   EMBL; AK079729; BAC37733.1; -; mRNA.
DR   EMBL; CH466545; EDL29280.1; -; Genomic_DNA.
DR   EMBL; BC080281; AAH80281.1; -; mRNA.
DR   EMBL; U53222; AAC52651.1; -; Genomic_DNA.
DR   CCDS; CCDS27480.1; -.
DR   RefSeq; NP_032242.3; NM_008216.3.
DR   AlphaFoldDB; P70312; -.
DR   SMR; P70312; -.
DR   BioGRID; 200210; 2.
DR   STRING; 10090.ENSMUSP00000062212; -.
DR   CAZy; GT2; Glycosyltransferase Family 2.
DR   GlyCosmos; P70312; 1 site, No reported glycans.
DR   GlyGen; P70312; 1 site.
DR   iPTMnet; P70312; -.
DR   PhosphoSitePlus; P70312; -.
DR   PaxDb; 10090-ENSMUSP00000062212; -.
DR   ProteomicsDB; 269513; -.
DR   Antibodypedia; 55587; 222 antibodies from 24 providers.
DR   DNASU; 15117; -.
DR   Ensembl; ENSMUST00000050544.8; ENSMUSP00000062212.8; ENSMUSG00000022367.8.
DR   GeneID; 15117; -.
DR   KEGG; mmu:15117; -.
DR   UCSC; uc007vsl.2; mouse.
DR   AGR; MGI:107821; -.
DR   CTD; 3037; -.
DR   MGI; MGI:107821; Has2.
DR   VEuPathDB; HostDB:ENSMUSG00000022367; -.
DR   eggNOG; KOG2571; Eukaryota.
DR   GeneTree; ENSGT00390000010337; -.
DR   HOGENOM; CLU_029695_3_0_1; -.
DR   InParanoid; P70312; -.
DR   OMA; KSATYVW; -.
DR   OrthoDB; 1361850at2759; -.
DR   PhylomeDB; P70312; -.
DR   TreeFam; TF332506; -.
DR   BRENDA; 2.4.1.212; 3474.
DR   Reactome; R-MMU-2142850; Hyaluronan biosynthesis and export.
DR   SABIO-RK; P70312; -.
DR   UniPathway; UPA00341; -.
DR   BioGRID-ORCS; 15117; 0 hits in 80 CRISPR screens.
DR   PRO; PR:P70312; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; P70312; Protein.
DR   Bgee; ENSMUSG00000022367; Expressed in vas deferens and 138 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IDA:CACAO.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR   GO; GO:1903561; C:extracellular vesicle; ISS:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0044853; C:plasma membrane raft; IDA:MGI.
DR   GO; GO:0050501; F:hyaluronan synthase activity; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0036302; P:atrioventricular canal development; IMP:UniProtKB.
DR   GO; GO:0060349; P:bone morphogenesis; IMP:MGI.
DR   GO; GO:0071498; P:cellular response to fluid shear stress; IEA:Ensembl.
DR   GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR   GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; ISO:MGI.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR   GO; GO:0090500; P:endocardial cushion to mesenchymal transition; IMP:UniProtKB.
DR   GO; GO:0044849; P:estrous cycle; IEA:Ensembl.
DR   GO; GO:0085029; P:extracellular matrix assembly; IDA:UniProtKB.
DR   GO; GO:0045226; P:extracellular polysaccharide biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0030213; P:hyaluronan biosynthetic process; IDA:MGI.
DR   GO; GO:0030212; P:hyaluronan metabolic process; IMP:MGI.
DR   GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; ISO:MGI.
DR   GO; GO:0051549; P:positive regulation of keratinocyte migration; ISO:MGI.
DR   GO; GO:0010838; P:positive regulation of keratinocyte proliferation; ISO:MGI.
DR   GO; GO:1900625; P:positive regulation of monocyte aggregation; ISO:MGI.
DR   GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR   GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISO:MGI.
DR   GO; GO:0035810; P:positive regulation of urine volume; ISS:UniProtKB.
DR   GO; GO:1901201; P:regulation of extracellular matrix assembly; ISO:MGI.
DR   GO; GO:0070295; P:renal water absorption; ISS:UniProtKB.
DR   GO; GO:0001570; P:vasculogenesis; IMP:UniProtKB.
DR   CDD; cd06434; GT2_HAS; 1.
DR   InterPro; IPR001173; Glyco_trans_2-like.
DR   InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR   PANTHER; PTHR22913; HYALURONAN SYNTHASE; 1.
DR   PANTHER; PTHR22913:SF7; HYALURONAN SYNTHASE 2; 1.
DR   Pfam; PF03142; Chitin_synth_2; 1.
DR   Pfam; PF00535; Glycos_transf_2; 1.
DR   SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
DR   Genevisible; P70312; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Endoplasmic reticulum; Glycoprotein; Glycosyltransferase;
KW   Golgi apparatus; Isopeptide bond; Lysosome; Membrane; Phosphoprotein;
KW   Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW   Ubl conjugation.
FT   CHAIN           1..552
FT                   /note="Hyaluronan synthase 2"
FT                   /id="PRO_0000197174"
FT   TOPO_DOM        1..11
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        12..32
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        33..45
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        46..66
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        67..374
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        375..395
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        396..402
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        403..423
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        424..429
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        430..450
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        451..475
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        476..496
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        497..510
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        511..531
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        532..552
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         110
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92819"
FT   MOD_RES         328
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92819"
FT   CARBOHYD        221
FT                   /note="O-linked (GlcNAc) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92819"
FT   CROSSLNK        190
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:Q92819"
FT   CONFLICT        138
FT                   /note="M -> I (in Ref. 1; AAC53309)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   552 AA;  63510 MW;  B840BABC6D2260D5 CRC64;
     MHCERFLCVL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG AFLASHLIIQ
     SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR KCLQSVKRLT YPGIKVVMVI
     DGNSDDDLYM MDIFSEVMGR DKSATYIWKN NFHEKGPGET EESHKESSQH VTQLVLSNKS
     ICIMQKWGGK REVMYTAFRA LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG
     DVQILNKYDS WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY
     NQEFMGNQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ QTRWSKSYFR
     EWLYNAMWFH KHHLWMTYEA VITGFFPFFL IATVIQLFYR GKIWNILLFL LTVQLVGLIK
     SSFASCLRGN IVMVFMSLYS VLYMSSLLPA KMFAIATINK AGWGTSGRKT IVVNFIGLIP
     VSVWFTILLG GVIFTIYKES KKPFSESKQT VLIVGTLIYA CYWVMLLTLY VVLINKCGRR
     KKGQQYDMVL DV
//