P_MOUSE
ID P_MOUSE Reviewed; 833 AA.
AC Q62052; Q0VBP9;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=P protein;
DE AltName: Full=Melanocyte-specific transporter protein;
DE AltName: Full=Pink-eyed dilution protein;
GN Name=Oca2; Synonyms=P;
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], TISSUE SPECIFICITY, AND DISEASE.
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=1509264; DOI=10.1126/science.257.5073.1121;
RA Gardner J.M., Nakatsu Y., Gondo Y., Lee S., Lyon M.F., King R.A.,
RA Brilliant M.H.;
RT "The mouse pink-eyed dilution gene: association with human Prader-Willi and
RT Angelman syndromes.";
RL Science 257:1121-1124(1992).
RN [2]
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 [3]
RP CHARACTERIZATION OF PROTEIN PRODUCT, AND SUBCELLULAR LOCATION.
RX PubMed=7991586; DOI=10.1073/pnas.91.25.12071;
RA Rosemblat S., Durham-Pierre D., Gardner J.M., Nakatsu Y., Brilliant M.H.,
RA Orlow S.J.;
RT "Identification of a melanosomal membrane protein encoded by the pink-eyed
RT dilution (type II oculocutaneous albinism) gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:12071-12075(1994).
RN [4]
RP FUNCTION.
RX PubMed=11310796; DOI=10.1034/j.1600-0749.2001.140203.x;
RA Brilliant M.H.;
RT "The mouse p (pink-eyed dilution) and human P genes, oculocutaneous
RT albinism type 2 (OCA2), and melanosomal pH.";
RL Pigment Cell Res. 14:86-93(2001).
RN [5]
RP INDUCTION OF MELANINE SYNTHESIS BY BAFILOMYCIN A1 ON P-NULL MELANOCYTES.
RX PubMed=11601658; DOI=10.1034/j.1600-0749.2001.140508.x;
RA Manga P., Orlow S.J.;
RT "Inverse correlation between pink-eyed dilution protein expression and
RT induction of melanogenesis by bafilomycin A1.";
RL Pigment Cell Res. 14:362-367(2001).
RN [6]
RP INVOLVEMENT IN POST-TRANSLATIONAL PROCESSING OF TYROSINASE.
RX PubMed=12058062; DOI=10.1091/mbc.02-02-0022.;
RA Chen K., Manga P., Orlow S.J.;
RT "Pink-eyed dilution protein controls the processing of tyrosinase.";
RL Mol. Biol. Cell 13:1953-1964(2002).
RN [7]
RP INVOLVEMENT IN INTRACELLULAR GLUTATHIONE METABOLISM.
RX PubMed=12475946; DOI=10.1091/mbc.e02-05-0282;
RA Staleva L., Manga P., Orlow S.J.;
RT "Pink-eyed dilution protein modulates arsenic sensitivity and intracellular
RT glutathione metabolism.";
RL Mol. Biol. Cell 13:4206-4220(2002).
CC -!- FUNCTION: Could be involved in the transport of tyrosine, the precursor
CC to melanin synthesis, within the melanocyte. Regulates the pH of
CC melanosome and the melanosome maturation. One of the components of the
CC mammalian pigmentary system. Seems to regulate the postranslational
CC processing of tyrosinase, which catalyzes the limiting reaction in
CC melanin synthesis. It can modulate intracellular glutathione
CC metabolism. {ECO:0000269|PubMed:11310796}.
CC -!- SUBCELLULAR LOCATION: Melanosome membrane {ECO:0000269|PubMed:7991586};
CC Multi-pass membrane protein {ECO:0000269|PubMed:7991586}.
CC -!- TISSUE SPECIFICITY: Most abundant in melanocytes. Also present in
CC neonatal and adult eye tissue presumably as a result of expression in
CC the retinal pigmented epithelium and choroid body, known sites of
CC melanogenesis in the eye. Small but detectable amounts also observed in
CC fetal, neonatal and adult brain. Moderate amounts detected in adult
CC testis and ovary. Not detected in heart, kidney, spleen, liver or
CC thymus. {ECO:0000269|PubMed:1509264}.
CC -!- DISEASE: Note=Defects in Oca2 are a cause of hypopigmentation of the
CC eyes, skin, and fur. The protein is missing or altered in six
CC independent mutant alleles of the OCA2 locus, suggesting that
CC disruption of this gene results in hypopigmentation phenotype that
CC defines mutant OCA2 alleles. {ECO:0000269|PubMed:1509264}.
CC -!- SIMILARITY: Belongs to the CitM (TC 2.A.11) transporter family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Questioning colour - Issue
CC 54 of January 2005;
CC URL="https://web.expasy.org/spotlight/back_issues/054";
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DR EMBL; M97900; AAA39908.1; -; mRNA.
DR EMBL; BC119220; AAI19221.1; -; mRNA.
DR EMBL; BC120549; AAI20550.1; -; mRNA.
DR CCDS; CCDS21319.1; -.
DR RefSeq; NP_068679.1; NM_021879.2.
DR RefSeq; XP_006540762.1; XM_006540699.1.
DR AlphaFoldDB; Q62052; -.
DR STRING; 10090.ENSMUSP00000032633; -.
DR GlyGen; Q62052; 3 sites.
DR iPTMnet; Q62052; -.
DR PhosphoSitePlus; Q62052; -.
DR PaxDb; Q62052; -.
DR PRIDE; Q62052; -.
DR ProteomicsDB; 300366; -.
DR Antibodypedia; 22329; 196 antibodies from 25 providers.
DR DNASU; 18431; -.
DR Ensembl; ENSMUST00000032633; ENSMUSP00000032633; ENSMUSG00000030450.
DR GeneID; 18431; -.
DR KEGG; mmu:18431; -.
DR UCSC; uc009hdy.1; mouse.
DR CTD; 4948; -.
DR MGI; MGI:97454; Oca2.
DR VEuPathDB; HostDB:ENSMUSG00000030450; -.
DR eggNOG; KOG2639; Eukaryota.
DR GeneTree; ENSGT01030000234550; -.
DR HOGENOM; CLU_011920_2_1_1; -.
DR InParanoid; Q62052; -.
DR OMA; ISWIDFE; -.
DR OrthoDB; 495573at2759; -.
DR PhylomeDB; Q62052; -.
DR TreeFam; TF323556; -.
DR Reactome; R-MMU-5662702; Melanin biosynthesis.
DR BioGRID-ORCS; 18431; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Oca2; mouse.
DR PRO; PR:Q62052; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q62052; protein.
DR Bgee; ENSMUSG00000030450; Expressed in iris and 53 other tissues.
DR ExpressionAtlas; Q62052; baseline and differential.
DR Genevisible; Q62052; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0033162; C:melanosome membrane; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0048066; P:developmental pigmentation; IMP:MGI.
DR GO; GO:0042438; P:melanin biosynthetic process; IMP:MGI.
DR GO; GO:0030318; P:melanocyte differentiation; IMP:MGI.
DR GO; GO:0043473; P:pigmentation; IMP:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:MGI.
DR GO; GO:0055085; P:transmembrane transport; IEA:InterPro.
DR InterPro; IPR004680; Cit_transptr-like_dom.
DR Pfam; PF03600; CitMHS; 1.
PE 1: Evidence at protein level;
KW Albinism; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..833
FT /note="P protein"
FT /id="PRO_0000172510"
FT TOPO_DOM 1..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..325
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..348
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..381
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 439..501
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 502..522
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 523..617
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 618..638
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 639
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 640..660
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 661..675
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 676..696
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 697..718
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 719..739
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 740..759
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 760..780
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 781..810
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 811..831
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 832..833
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 269
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 833 AA; 91869 MW; 41B9F6491EFAFEE3 CRC64;
MRLENKDIRL ASAVLEVELH QTSALSVPTC PDPGRLLTVK PATSNYKLGQ ADPCIPYAGE
AAGKSVCVPE HTEFGSFLVK GSSSLKDLSF KEDTPLLWNS SQKKRSQLMP VHHPEFIATE
GSWENGLTAW EQKCMLGKEV ADLSALASSE KRDLAGSVHL RAQVSKLGCC VRWIKITGLF
VFVVLCSILF SLYPDQGKFW QLLAVSPLEN YSVNLSGHAD SMILQLDLAG ALMAGGPSGS
GKEEHVVVVV TQTDAAGNRR RRPQQLTYNW TVLLNPRSEH VVVSRTFEIV SREAVSISIQ
ASLQQTRLVP LLLAHQFLGA SVEAQVASAV AILAGVYTLI IFEIVHRTLA AMLGALAALA
ALAVVGDRPS LTHVVEWIDF ETLALLFGMM ILVAVFSETG FFDYCAVKAY QLSRGRVWAM
IFMLCLMAAI LSAFLDNVTT MLLFTPVTIR LCEVLNLDPR QVLIAEVIFT NIGGAATAIG
DPPNVIIVSN QELRKMGLDF AGFTAHMFLG ICLVLLVSFP LLRLLYWNKK LYNKEPSEIV
ELKHEIHVWR LTAQRISPAS REETAVRGLL LEKVLALEHL LAQRLHTFHR QISQEDKNWE
TNIQELQRKH RISDRSLLVK CLTVLGFVIS MFFLNSFVPG IHLDLGWIAI LGAIWLLILA
DIHDFEIILH RVEWATLLFF AALFVLMEAL THLHLVEYVG EQTALLIKMV PEDQRFAAAI
VLIVWVSALA SSLIDNIPFT ATMIPVLLNL SQDPEISLPA LPLMYALALG ACLGGNGTLI
GASTNVVCAG IAEKHGYGFS FMEFFRLGFP VMLMSCTIGM CYLLIAHIVV GWN
