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Q96EY5 (MB12A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Multivesicular body subunit 12A
Alternative name(s):
CIN85/CD2AP family-binding protein
ESCRT-I complex subunit MVB12A
Protein FAM125A
Gene names
Name:MVB12A
Synonyms:CFBP, FAM125A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length273 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor. Ref.2

Subunit structure

Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoechiometry. Interacts with CD2AP and CIN85/SH3KBP1. Interacts with CD2AP (via one of the SH3 domains). Interacts with TSG101; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS28. Interacts with VPS37B; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37C; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with CEP55. Ref.2 Ref.4 Ref.5

Subcellular location

Cytoplasm. Nucleus. Endosome. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Late endosome membrane; Peripheral membrane protein Probable. Note: Colocalizes with F-actin. Some fraction may be nuclear. Ref.2 Ref.4

Tissue specificity

Ubiquitously expressed except in skeletal muscle. Ref.2

Post-translational modification

Phosphorylated on Tyr-204 upon EGF stimulation. Phosphorylation is required for interaction with CD2AP and CIN85/SH3KBP1. Ref.2 Ref.4

Sequence similarities

Belongs to the MVB12 family.

Contains 1 MABP domain.

Contains 1 UMA domain.

Ontologies

Keywords
   Biological processProtein transport
Transport
   Cellular componentCytoplasm
Cytoskeleton
Endosome
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processprotein transport

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of epidermal growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 20654576. Source: UniProt

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Inferred by curator PubMed 20654576. Source: UniProt

   Cellular_componentESCRT I complex

Inferred from direct assay PubMed 20654576PubMed 22232651. Source: UniProt

aggresome

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Inferred from direct assay PubMed 20654576. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

late endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay. Source: HPA

vesicle

Inferred from direct assay PubMed 20654576. Source: UniProt

   Molecular_functionlipid binding

Inferred from mutant phenotype PubMed 22232651. Source: UniProt

protein binding

Inferred from physical interaction PubMed 20654576. Source: UniProt

ubiquitin binding

Inferred from mutant phenotype PubMed 20654576. Source: UniProt

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96EY5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96EY5-2)

Also known as: Delta 5;

The sequence of this isoform differs from the canonical sequence as follows:
     139-178: Missing.
Note: Does not interact with CD2AP.
Isoform 3 (identifier: Q96EY5-3)

Also known as: Delta 8;

The sequence of this isoform differs from the canonical sequence as follows:
     238-253: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 273273Multivesicular body subunit 12A
PRO_0000249069

Regions

Domain9 – 151143MABP
Domain215 – 26551UMA
Region192 – 27382Interaction with TSG101, VPS37B and VPS28
Motif155 – 1606SH3-binding

Amino acid modifications

Modified residue1301Phosphothreonine Ref.4
Modified residue1631Phosphoserine Ref.4
Modified residue1701Phosphoserine Ref.4 Ref.6 Ref.7 Ref.8
Modified residue2021Phosphoserine Ref.8
Modified residue2041Phosphotyrosine Ref.2
Modified residue2071Phosphoserine Ref.4
Modified residue2321Phosphoserine Ref.4

Natural variations

Alternative sequence139 – 17840Missing in isoform 2.
VSP_020629
Alternative sequence238 – 25316Missing in isoform 3.
VSP_020630
Natural variant1061C → Y.
Corresponds to variant rs34949802 [ dbSNP | Ensembl ].
VAR_049018

Experimental info

Mutagenesis2041Y → D: Mimics constitutively phosphorylated form and has the ability to interact with CD2AP and CIN85/SH3KBP1 without EGF treatment. Ref.2
Mutagenesis2041Y → F: Abolishes interaction with CD2AP and CIN85/SH3KBP1. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 7C765A0E96DC0F45

FASTA27328,783
        10         20         30         40         50         60 
MDPVPGTDSA PLAGLAWSSA SAPPPRGFSA ISCTVEGAPA SFGKSFAQKS GYFLCLSSLG 

        70         80         90        100        110        120 
SLENPQENVV ADIQIVVDKS PLPLGFSPVC DPMDSKASVS KKKRMCVKLL PLGATDTAVF 

       130        140        150        160        170        180 
DVRLSGKTKT VPGYLRIGDM GGFAIWCKKA KAPRPVPKPR GLSRDMQGLS LDAASQPSKG 

       190        200        210        220        230        240 
GLLERTASRL GSRASTLRRN DSIYEASSLY GISAMDGVPF TLHPRFEGKS CSPLAFSAFG 

       250        260        270 
DLTIKSLADI EEEYNYGFVV EKTAAARLPP SVS 

« Hide

Isoform 2 (Delta 5) [UniParc].

Checksum: E5E04F5CFBC399C4
Show »

FASTA23324,532
Isoform 3 (Delta 8) [UniParc].

Checksum: CE551F6F2AA734C9
Show »

FASTA25727,050

References

« Hide 'large scale' references
[1]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas and Uterus.
[2]"CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP."
Konishi H., Tashiro K., Murata Y., Nabeshi H., Yamauchi E., Taniguchi H.
J. Biol. Chem. 281:28919-28931(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-204, TISSUE SPECIFICITY, INTERACTION WITH CD2AP AND SH3KBP1, MUTAGENESIS OF TYR-204.
[3]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[4]"Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding."
Morita E., Sandrin V., Alam S.L., Eckert D.M., Gygi S.P., Sundquist W.I.
Cell Host Microbe 2:41-53(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSG101; VPS28; VPS37B; VPS37C AND VPS37D, IDENTIFICATION IN THE ESCRT-I COMPLEX, RECONSTITUTION OF THE ESCRT-I COMPLEX, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-130; SER-163; SER-170; SER-207 AND SER-232, IDENTIFICATION BY MASS SPECTROMETRY.
[5]"Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis."
Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P., Rodesch C.K., Sundquist W.I.
EMBO J. 26:4215-4227(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CEP55.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170 AND SER-202, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC007883 mRNA. Translation: AAH07883.2.
BC011840 mRNA. Translation: AAH11840.1.
CCDSCCDS12359.1. [Q96EY5-1]
RefSeqNP_612410.1. NM_138401.2. [Q96EY5-1]
UniGeneHs.515243.

3D structure databases

ProteinModelPortalQ96EY5.
SMRQ96EY5. Positions 11-146.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125018. 10 interactions.
IntActQ96EY5. 1 interaction.
STRING9606.ENSP00000324810.

PTM databases

PhosphoSiteQ96EY5.

Polymorphism databases

DMDM74731632.

Proteomic databases

MaxQBQ96EY5.
PaxDbQ96EY5.
PRIDEQ96EY5.

Protocols and materials databases

DNASU93343.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317040; ENSP00000324810; ENSG00000141971. [Q96EY5-1]
ENST00000392702; ENSP00000376466; ENSG00000141971. [Q96EY5-2]
ENST00000543795; ENSP00000444653; ENSG00000141971. [Q96EY5-1]
GeneID93343.
KEGGhsa:93343.
UCSCuc002ngo.1. human. [Q96EY5-1]

Organism-specific databases

CTD93343.
GeneCardsGC19P017605.
HGNCHGNC:25153. MVB12A.
HPAHPA041885.
HPA042231.
neXtProtNX_Q96EY5.
PharmGKBPA162385826.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG301965.
HOGENOMHOG000231822.
HOVERGENHBG055538.
InParanoidQ96EY5.
KOK12186.
OMAIENEYNY.
OrthoDBEOG7K3TMB.
PhylomeDBQ96EY5.
TreeFamTF314477.

Gene expression databases

ArrayExpressQ96EY5.
BgeeQ96EY5.
CleanExHS_FAM125A.
GenevestigatorQ96EY5.

Family and domain databases

InterProIPR018798. FAM125.
IPR023341. MABP.
IPR023340. UMA.
[Graphical view]
PfamPF10240. DUF2464. 1 hit.
[Graphical view]
PROSITEPS51498. MABP. 1 hit.
PS51497. UMA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFAM125A. human.
GenomeRNAi93343.
NextBio78049.
PMAP-CutDBQ96EY5.
PROQ96EY5.

Entry information

Entry nameMB12A_HUMAN
AccessionPrimary (citable) accession number: Q96EY5
Secondary accession number(s): Q96I18
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM