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 28-JAN-2026, entry version 171. 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; Q9UHD4: CIDEB; NbExp=2; IntAct=EBI-4290865, EBI-7062247; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC007883; AAH07883.2; -; mRNA. DR EMBL; BC011840; AAH11840.1; -; mRNA. DR CCDS; CCDS12359.1; -. [Q96EY5-1] DR RefSeq; NP_612410.1; NM_138401.4. [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; 66. 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 FunCoup; Q96EY5; 1273. DR IntAct; Q96EY5; 46. DR MINT; Q96EY5; -. DR STRING; 9606.ENSP00000324810; -. DR iPTMnet; Q96EY5; -. DR MetOSite; Q96EY5; -. DR PhosphoSitePlus; Q96EY5; -. DR BioMuta; MVB12A; -. DR DMDM; 74731632; -. DR jPOST; Q96EY5; -. DR MassIVE; Q96EY5; -. DR PaxDb; 9606-ENSP00000324810; -. DR PeptideAtlas; Q96EY5; -. DR ProteomicsDB; 76469; -. [Q96EY5-1] DR ProteomicsDB; 76470; -. [Q96EY5-2] DR ProteomicsDB; 76471; -. [Q96EY5-3] DR Pumba; Q96EY5; -. DR Antibodypedia; 51512; 32 antibodies from 12 providers. DR DNASU; 93343; -. DR Ensembl; ENST00000317040.12; ENSP00000324810.6; ENSG00000141971.15. [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 AGR; HGNC:25153; -. DR ClinPGx; PA162385826; -. DR CTD; 93343; -. DR DisGeNET; 93343; -. DR GeneCards; MVB12A; -. DR HGNC; HGNC:25153; MVB12A. DR HPA; ENSG00000141971; Low tissue specificity. DR OpenTargets; ENSG00000141971; -. DR VEuPathDB; HostDB:ENSG00000141971; -. DR eggNOG; KOG4000; Eukaryota. DR GeneTree; ENSGT00940000160542; -. DR HOGENOM; CLU_064823_2_0_1; -. DR InParanoid; Q96EY5; -. DR OMA; KYGYYLC; -. DR OrthoDB; 6021306at2759; -. DR PAN-GO; Q96EY5; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q96EY5; -. 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 Agora; ENSG00000141971; -. DR BioGRID-ORCS; 93343; 20 hits in 1161 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 141 other cell types or tissues. DR ExpressionAtlas; Q96EY5; baseline and differential. 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: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; NAS: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; NAS: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 FunFam; 2.100.10.50:FF:000003; Multivesicular body subunit 12A; 1. DR Gene3D; 2.100.10.50; -; 1. DR InterPro; IPR023341; MABP. DR InterPro; IPR040335; MVB12A. DR InterPro; IPR018798; MVB12A/B. DR InterPro; IPR023340; UMA. DR PANTHER; PTHR31612; MULTIVESICULAR BODY SUBUNIT 12A; 1. DR PANTHER; PTHR31612:SF2; MULTIVESICULAR BODY SUBUNIT 12A; 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; KW Proteomics identification; Reference proteome; 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 //