MB12A_HUMAN
ID MB12A_HUMAN Reviewed; 273 AA.
AC Q96EY5; Q96I18;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Multivesicular body subunit 12A;
DE AltName: Full=CIN85/CD2AP family-binding protein;
DE AltName: Full=ESCRT-I complex subunit MVB12A;
DE AltName: Full=Protein FAM125A;
GN Name=MVB12A; Synonyms=CFBP, FAM125A;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas, and Uterus;
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 [2]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, ALTERNATIVE SPLICING
RP (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-204,
RP TISSUE SPECIFICITY, INTERACTION WITH CD2AP AND SH3KBP1, AND MUTAGENESIS OF
RP TYR-204.
RX PubMed=16895919; DOI=10.1074/jbc.m605693200;
RA Konishi H., Tashiro K., Murata Y., Nabeshi H., Yamauchi E., Taniguchi H.;
RT "CFBP is a novel tyrosine-phosphorylated protein that might function as a
RT regulator of CIN85/CD2AP.";
RL J. Biol. Chem. 281:28919-28931(2006).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [4]
RP INTERACTION WITH TSG101; VPS28; VPS37B; VPS37C AND VPS37D, IDENTIFICATION
RP IN THE ESCRT-I COMPLEX, RECONSTITUTION OF THE ESCRT-I COMPLEX, SUBCELLULAR
RP LOCATION, PHOSPHORYLATION AT THR-130; SER-163; SER-170; SER-207 AND
RP SER-232, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18005716; DOI=10.1016/j.chom.2007.06.003;
RA Morita E., Sandrin V., Alam S.L., Eckert D.M., Gygi S.P., Sundquist W.I.;
RT "Identification of human MVB12 proteins as ESCRT-I subunits that function
RT in HIV budding.";
RL Cell Host Microbe 2:41-53(2007).
RN [5]
RP INTERACTION WITH CEP55.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P., Rodesch C.K.,
RA Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody and
RT function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170 AND SER-202, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; SER-195 AND SER-202, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Component of the ESCRT-I complex, a regulator of vesicular
CC trafficking process. Required for the sorting of endocytic
CC ubiquitinated cargos into multivesicular bodies. May be involved in the
CC ligand-mediated internalization and down-regulation of EGF receptor.
CC {ECO:0000269|PubMed:16895919}.
CC -!- SUBUNIT: Component of the ESCRT-I complex (endosomal sorting complex
CC required for transport I) which consists of TSG101, VPS28, a VPS37
CC protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry.
CC Interacts with CD2AP and CIN85/SH3KBP1. Interacts with CD2AP (via one
CC of the SH3 domains). Interacts with TSG101; the association appears to
CC be mediated by the TSG101-VPS37 binary subcomplex. Interacts with
CC VPS28. Interacts with VPS37B; the association appears to be mediated by
CC the TSG101-VPS37 binary subcomplex. Interacts with VPS37C; the
CC association appears to be mediated by the TSG101-VPS37 binary
CC subcomplex. Interacts with VPS37D; the association appears to be
CC mediated by the TSG101-VPS37 binary subcomplex. Interacts with CEP55.
CC {ECO:0000269|PubMed:16895919, ECO:0000269|PubMed:17853893,
CC ECO:0000269|PubMed:18005716}.
CC -!- INTERACTION:
CC Q96EY5; O75031: HSF2BP; NbExp=3; IntAct=EBI-4290865, EBI-7116203;
CC Q96EY5; Q86WC6: PPP1R27; NbExp=3; IntAct=EBI-4290865, EBI-5235602;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Endosome. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome. Late endosome
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Colocalizes with F-actin. Some fraction may be nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96EY5-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta 5;
CC IsoId=Q96EY5-2; Sequence=VSP_020629;
CC Name=3; Synonyms=Delta 8;
CC IsoId=Q96EY5-3; Sequence=VSP_020630;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed except in skeletal muscle.
CC {ECO:0000269|PubMed:16895919}.
CC -!- PTM: Phosphorylated on Tyr-204 upon EGF stimulation. Phosphorylation is
CC required for interaction with CD2AP and CIN85/SH3KBP1.
CC {ECO:0000269|PubMed:16895919, ECO:0000269|PubMed:18005716}.
CC -!- MISCELLANEOUS: [Isoform 2]: Does not interact with CD2AP.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the MVB12 family. {ECO:0000305}.
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DR EMBL; BC007883; AAH07883.2; -; mRNA.
DR EMBL; BC011840; AAH11840.1; -; mRNA.
DR CCDS; CCDS12359.1; -. [Q96EY5-1]
DR RefSeq; NP_612410.1; NM_138401.3. [Q96EY5-1]
DR PDB; 6VME; X-ray; 2.19 A; A/D/P/Q/R/T=206-228.
DR PDBsum; 6VME; -.
DR AlphaFoldDB; Q96EY5; -.
DR SMR; Q96EY5; -.
DR BioGRID; 125018; 49.
DR ComplexPortal; CPX-2505; ESCRT-I complex, VPS37B-MVB12A variant.
DR ComplexPortal; CPX-7147; ESCRT-I complex, VPS37C-MVB12A variant.
DR ComplexPortal; CPX-7148; ESCRT-I complex, VPS37D-MVB12A variant.
DR ComplexPortal; CPX-7162; ESCRT-I complex, VPS37A-MVB12A variant.
DR IntAct; Q96EY5; 24.
DR MINT; Q96EY5; -.
DR STRING; 9606.ENSP00000324810; -.
DR iPTMnet; Q96EY5; -.
DR MetOSite; Q96EY5; -.
DR PhosphoSitePlus; Q96EY5; -.
DR BioMuta; MVB12A; -.
DR DMDM; 74731632; -.
DR EPD; Q96EY5; -.
DR jPOST; Q96EY5; -.
DR MassIVE; Q96EY5; -.
DR MaxQB; Q96EY5; -.
DR PaxDb; Q96EY5; -.
DR PeptideAtlas; Q96EY5; -.
DR PRIDE; Q96EY5; -.
DR ProteomicsDB; 76469; -. [Q96EY5-1]
DR ProteomicsDB; 76470; -. [Q96EY5-2]
DR ProteomicsDB; 76471; -. [Q96EY5-3]
DR Antibodypedia; 51512; 35 antibodies from 11 providers.
DR DNASU; 93343; -.
DR Ensembl; ENST00000317040.12; ENSP00000324810.6; ENSG00000141971.13. [Q96EY5-1]
DR Ensembl; ENST00000543795.5; ENSP00000444653.1; ENSG00000141971.13. [Q96EY5-1]
DR GeneID; 93343; -.
DR KEGG; hsa:93343; -.
DR MANE-Select; ENST00000317040.12; ENSP00000324810.6; NM_138401.4; NP_612410.1.
DR UCSC; uc002ngo.2; human. [Q96EY5-1]
DR CTD; 93343; -.
DR DisGeNET; 93343; -.
DR GeneCards; MVB12A; -.
DR HGNC; HGNC:25153; MVB12A.
DR HPA; ENSG00000141971; Low tissue specificity.
DR neXtProt; NX_Q96EY5; -.
DR OpenTargets; ENSG00000141971; -.
DR PharmGKB; PA162385826; -.
DR VEuPathDB; HostDB:ENSG00000141971; -.
DR eggNOG; KOG4000; Eukaryota.
DR GeneTree; ENSGT00940000160542; -.
DR HOGENOM; CLU_064823_2_0_1; -.
DR InParanoid; Q96EY5; -.
DR OMA; EYNYTFA; -.
DR PhylomeDB; Q96EY5; -.
DR TreeFam; TF314477; -.
DR PathwayCommons; Q96EY5; -.
DR Reactome; R-HSA-162588; Budding and maturation of HIV virion.
DR Reactome; R-HSA-174490; Membrane binding and targetting of GAG proteins.
DR Reactome; R-HSA-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR Reactome; R-HSA-9610379; HCMV Late Events.
DR Reactome; R-HSA-9615710; Late endosomal microautophagy.
DR SignaLink; Q96EY5; -.
DR BioGRID-ORCS; 93343; 18 hits in 1083 CRISPR screens.
DR ChiTaRS; MVB12A; human.
DR GenomeRNAi; 93343; -.
DR Pharos; Q96EY5; Tbio.
DR PRO; PR:Q96EY5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96EY5; protein.
DR Bgee; ENSG00000141971; Expressed in right ovary and 139 other tissues.
DR ExpressionAtlas; Q96EY5; baseline and differential.
DR Genevisible; Q96EY5; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0000813; C:ESCRT I complex; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IMP:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0043130; F:ubiquitin binding; IMP:UniProtKB.
DR GO; GO:0032510; P:endosome to lysosome transport via multivesicular body sorting pathway; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0090148; P:membrane fission; IC:ComplexPortal.
DR GO; GO:0036258; P:multivesicular body assembly; TAS:ParkinsonsUK-UCL.
DR GO; GO:0043328; P:protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IC:ComplexPortal.
DR GO; GO:0032801; P:receptor catabolic process; IBA:GO_Central.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IC:UniProtKB.
DR GO; GO:0046755; P:viral budding; IMP:UniProtKB.
DR GO; GO:0039702; P:viral budding via host ESCRT complex; TAS:ParkinsonsUK-UCL.
DR GO; GO:0019075; P:virus maturation; IMP:UniProtKB.
DR InterPro; IPR023341; MABP.
DR InterPro; IPR040335; MVB12A.
DR InterPro; IPR018798; MVB12A/B.
DR InterPro; IPR023340; UMA.
DR PANTHER; PTHR31612; PTHR31612; 1.
DR Pfam; PF10240; DUF2464; 1.
DR PROSITE; PS51498; MABP; 1.
DR PROSITE; PS51497; UMA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Cytoskeleton; Endosome;
KW Membrane; Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW SH3-binding; Transport.
FT CHAIN 1..273
FT /note="Multivesicular body subunit 12A"
FT /id="PRO_0000249069"
FT DOMAIN 9..151
FT /note="MABP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00831"
FT DOMAIN 215..265
FT /note="UMA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00830"
FT REGION 192..273
FT /note="Interaction with TSG101, VPS37B and VPS28"
FT /evidence="ECO:0000269|PubMed:18005716"
FT MOTIF 155..160
FT /note="SH3-binding"
FT MOD_RES 130
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18005716"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18005716"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18005716,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 204
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16895919"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18005716"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18005716"
FT VAR_SEQ 139..178
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_020629"
FT VAR_SEQ 238..253
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_020630"
FT VARIANT 106
FT /note="C -> Y (in dbSNP:rs34949802)"
FT /id="VAR_049018"
FT MUTAGEN 204
FT /note="Y->D: Mimics constitutively phosphorylated form and
FT has the ability to interact with CD2AP and CIN85/SH3KBP1
FT without EGF treatment."
FT /evidence="ECO:0000269|PubMed:16895919"
FT MUTAGEN 204
FT /note="Y->F: Abolishes interaction with CD2AP and
FT CIN85/SH3KBP1."
FT /evidence="ECO:0000269|PubMed:16895919"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:6VME"
FT HELIX 212..215
FT /evidence="ECO:0007829|PDB:6VME"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:6VME"
SQ SEQUENCE 273 AA; 28783 MW; 7C765A0E96DC0F45 CRC64;
MDPVPGTDSA PLAGLAWSSA SAPPPRGFSA ISCTVEGAPA SFGKSFAQKS GYFLCLSSLG
SLENPQENVV ADIQIVVDKS PLPLGFSPVC DPMDSKASVS KKKRMCVKLL PLGATDTAVF
DVRLSGKTKT VPGYLRIGDM GGFAIWCKKA KAPRPVPKPR GLSRDMQGLS LDAASQPSKG
GLLERTASRL GSRASTLRRN DSIYEASSLY GISAMDGVPF TLHPRFEGKS CSPLAFSAFG
DLTIKSLADI EEEYNYGFVV EKTAAARLPP SVS
