UPK3A_HUMAN
ID UPK3A_HUMAN Reviewed; 287 AA.
AC O75631; B0QY25; O60261; Q32N05; Q5TII6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Uroplakin-3a;
DE Short=UP3a;
DE AltName: Full=Uroplakin III;
DE Short=UPIII;
DE Flags: Precursor;
GN Name=UPK3A; Synonyms=UPK3;
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).
RC TISSUE=Ureter;
RA Geall K., Hall G., Smith B., Southgate J.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-154.
RC TISSUE=Urinary bladder urothelium;
RX PubMed=9818021; DOI=10.1111/j.1349-7006.1998.tb00643.x;
RA Yuasa T., Yoshiki T., Tanaka T., Kim C.J., Isono T., Okada Y.;
RT "Expression of uroplakin Ib and uroplakin III genes in tissues and
RT peripheral blood of patients with transitional cell carcinoma.";
RL Jpn. J. Cancer Res. 89:879-882(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 TISSUE SPECIFICITY.
RX PubMed=9846985; DOI=10.1016/s0002-9440(10)65709-4;
RA Lobban E.D., Smith B.A., Hall G.D., Harnden P., Roberts P., Selby P.J.,
RA Trejdosiewicz L.K., Southgate J.;
RT "Uroplakin gene expression by normal and neoplastic human urothelium.";
RL Am. J. Pathol. 153:1957-1967(1998).
RN [7]
RP VARIANT LEU-273, POSSIBLE INVOLVEMENT IN KIDNEY AND URINARY TRACT
RP ANOMALIES, AND CHARACTERIZATION OF VARIANT LEU-273.
RX PubMed=15888565; DOI=10.1681/asn.2004090776;
RA Jenkins D., Bitner-Glindzicz M., Malcolm S., Hu C.-C.A., Allison J.,
RA Winyard P.J.D., Gullett A.M., Thomas D.F.M., Belk R.A., Feather S.A.,
RA Sun T.-T., Woolf A.S.;
RT "De novo Uroplakin IIIa heterozygous mutations cause human renal adysplasia
RT leading to severe kidney failure.";
RL J. Am. Soc. Nephrol. 16:2141-2149(2005).
RN [8]
RP VARIANT ASP-202, AND POSSIBLE INVOLVEMENT IN KIDNEY AND URINARY TRACT
RP ANOMALIES.
RX PubMed=16731295; DOI=10.1053/j.ajkd.2006.02.177;
RA Schoenfelder E.-M., Knueppel T., Tasic V., Miljkovic P., Konrad M.,
RA Wuehl E., Antignac C., Bakkaloglu A., Schaefer F., Weber S.;
RT "Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in
RT humans.";
RL Am. J. Kidney Dis. 47:1004-1012(2006).
CC -!- FUNCTION: Component of the asymmetric unit membrane (AUM); a highly
CC specialized biomembrane elaborated by terminally differentiated
CC urothelial cells. May play an important role in AUM-cytoskeleton
CC interaction in terminally differentiated urothelial cells. It also
CC contributes to the formation of urothelial glycocalyx which may play an
CC important role in preventing bacterial adherence (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer with uroplakin-1B (UPK1B). {ECO:0000250}.
CC -!- INTERACTION:
CC O75631; O43765: SGTA; NbExp=3; IntAct=EBI-10188907, EBI-347996;
CC O75631; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-10188907, EBI-744081;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}. Note=Heterodimer
CC formation with UPK1B is a prerequisite to exit out of the endoplasmic
CC reticulum (ER). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75631-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75631-2; Sequence=VSP_030004;
CC -!- TISSUE SPECIFICITY: Expressed in ureter. {ECO:0000269|PubMed:9846985}.
CC -!- DISEASE: Note=Mutations in UPK3A have been detected in patients with
CC renal adyplasia suggesting a possible involvement of this gene in
CC kidney and urinary tract anomalies.
CC -!- SIMILARITY: Belongs to the uroplakin-3 family. {ECO:0000305}.
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DR EMBL; AF085808; AAC34888.1; -; mRNA.
DR EMBL; AB010637; BAA31460.1; -; mRNA.
DR EMBL; AB010116; BAA25678.1; -; mRNA.
DR EMBL; CR456608; CAG30494.1; -; mRNA.
DR EMBL; AL008718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069544; AAH69544.1; -; mRNA.
DR EMBL; BC108900; AAI08901.1; -; mRNA.
DR CCDS; CCDS14064.1; -. [O75631-1]
DR CCDS; CCDS54539.1; -. [O75631-2]
DR RefSeq; NP_001161046.1; NM_001167574.1. [O75631-2]
DR RefSeq; NP_008884.1; NM_006953.3. [O75631-1]
DR AlphaFoldDB; O75631; -.
DR BioGRID; 113226; 3.
DR IntAct; O75631; 2.
DR STRING; 9606.ENSP00000216211; -.
DR TCDB; 8.A.90.2.1; the uroplakin 2/3 (upk2/3) family.
DR GlyGen; O75631; 3 sites.
DR iPTMnet; O75631; -.
DR PhosphoSitePlus; O75631; -.
DR BioMuta; UPK3A; -.
DR jPOST; O75631; -.
DR MassIVE; O75631; -.
DR PaxDb; O75631; -.
DR PeptideAtlas; O75631; -.
DR PRIDE; O75631; -.
DR ProteomicsDB; 50129; -. [O75631-1]
DR ProteomicsDB; 50130; -. [O75631-2]
DR Antibodypedia; 13681; 267 antibodies from 26 providers.
DR DNASU; 7380; -.
DR Ensembl; ENST00000216211.9; ENSP00000216211.4; ENSG00000100373.10. [O75631-1]
DR Ensembl; ENST00000396082.2; ENSP00000379391.2; ENSG00000100373.10. [O75631-2]
DR GeneID; 7380; -.
DR KEGG; hsa:7380; -.
DR MANE-Select; ENST00000216211.9; ENSP00000216211.4; NM_006953.4; NP_008884.1.
DR UCSC; uc003bfy.4; human. [O75631-1]
DR CTD; 7380; -.
DR DisGeNET; 7380; -.
DR GeneCards; UPK3A; -.
DR HGNC; HGNC:12580; UPK3A.
DR HPA; ENSG00000100373; Group enriched (prostate, skeletal muscle, urinary bladder).
DR MalaCards; UPK3A; -.
DR MIM; 611559; gene.
DR neXtProt; NX_O75631; -.
DR OpenTargets; ENSG00000100373; -.
DR Orphanet; 93100; Renal agenesis, unilateral.
DR PharmGKB; PA37212; -.
DR VEuPathDB; HostDB:ENSG00000100373; -.
DR eggNOG; ENOG502S14V; Eukaryota.
DR GeneTree; ENSGT00940000153392; -.
DR HOGENOM; CLU_082608_1_0_1; -.
DR InParanoid; O75631; -.
DR OMA; EKPFCVF; -.
DR OrthoDB; 577034at2759; -.
DR PhylomeDB; O75631; -.
DR TreeFam; TF336628; -.
DR PathwayCommons; O75631; -.
DR SignaLink; O75631; -.
DR BioGRID-ORCS; 7380; 6 hits in 1068 CRISPR screens.
DR ChiTaRS; UPK3A; human.
DR GeneWiki; UPK3A; -.
DR GenomeRNAi; 7380; -.
DR Pharos; O75631; Tbio.
DR PRO; PR:O75631; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O75631; protein.
DR Bgee; ENSG00000100373; Expressed in gastrocnemius and 91 other tissues.
DR Genevisible; O75631; HS.
DR GO; GO:0120001; C:apical plasma membrane urothelial plaque; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0055075; P:potassium ion homeostasis; IEA:Ensembl.
DR GO; GO:0055078; P:sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0015840; P:urea transport; IBA:GO_Central.
DR GO; GO:0060157; P:urinary bladder development; IEA:Ensembl.
DR GO; GO:0006833; P:water transport; IBA:GO_Central.
DR InterPro; IPR024831; Uroplakin-3.
DR InterPro; IPR024825; Uroplakin-3a.
DR PANTHER; PTHR15446; PTHR15446; 1.
DR PANTHER; PTHR15446:SF17; PTHR15446:SF17; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Endoplasmic reticulum; Glycoprotein;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT CHAIN 19..287
FT /note="Uroplakin-3a"
FT /id="PRO_0000022637"
FT TOPO_DOM 19..207
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..287
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 242..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 70..191
FT /note="AISRNASVQDSTNTPLGSTFLQTEGGRTGPYKAVAFDLIPCSDLPSLDAIGD
FT VSKASQILNAYLVRVGANGTCLWDPNFQGLCNAPLSAATEYRFKYVLVNMSTGLVEDQT
FT LWSDPIRTNQL -> V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030004"
FT VARIANT 91
FT /note="Q -> L (in dbSNP:rs6006979)"
FT /id="VAR_044399"
FT VARIANT 154
FT /note="A -> P (in dbSNP:rs1057353)"
FT /evidence="ECO:0000269|PubMed:9818021"
FT /id="VAR_020158"
FT VARIANT 202
FT /note="G -> D (found in a patient with unilateral
FT multicystic kidney disease; unknown pathological
FT significance; dbSNP:rs121918187)"
FT /evidence="ECO:0000269|PubMed:16731295"
FT /id="VAR_044400"
FT VARIANT 273
FT /note="P -> L (found in patients with renal adysplasia;
FT unknown pathological significance; normal targeting to the
FT cell surface; dbSNP:rs121918186)"
FT /evidence="ECO:0000269|PubMed:15888565"
FT /id="VAR_044401"
FT CONFLICT 236
FT /note="D -> A (in Ref. 2; BAA31460/BAA25678)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 287 AA; 30670 MW; 2A14B21746FDBD25 CRC64;
MPPLWALLAL GCLRFGSAVN LQPQLASVTF ATNNPTLTTV ALEKPLCMFD SKEALTGTHE
VYLYVLVDSA ISRNASVQDS TNTPLGSTFL QTEGGRTGPY KAVAFDLIPC SDLPSLDAIG
DVSKASQILN AYLVRVGANG TCLWDPNFQG LCNAPLSAAT EYRFKYVLVN MSTGLVEDQT
LWSDPIRTNQ LTPYSTIDTW PGRRSGGMIV ITSILGSLPF FLLVGFAGAI ALSLVDMGSS
DGETTHDSQI TQEAVPKSLG ASESSYTSVN RGPPLDRAEV YSSKLQD
