Q96EY5 (MB12A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	273 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Cytoplasm › cytoskeleton › centrosome. 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 process	Protein transport Transport
Cellular component	Cytoplasm Cytoskeleton Endosome Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	aggresome Inferred from direct assay. Source: HPA cytoplasm 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
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 273	273	Multivesicular body subunit 12A		PRO_0000249069
Regions
	Domain	9 – 151	143	MABP
	Domain	215 – 265	51	UMA
	Region	192 – 273	82	Interaction with TSG101, VPS37B and VPS28
	Motif	155 – 160	6	SH3-binding
Amino acid modifications
	Modified residue	130	1	Phosphothreonine Ref.4
	Modified residue	163	1	Phosphoserine Ref.4
	Modified residue	170	1	Phosphoserine Ref.4 Ref.6 Ref.7 Ref.8
	Modified residue	202	1	Phosphoserine Ref.8
	Modified residue	204	1	Phosphotyrosine Ref.2
	Modified residue	207	1	Phosphoserine Ref.4
	Modified residue	232	1	Phosphoserine Ref.4
Natural variations
	Alternative sequence	139 – 178	40	Missing in isoform 2.		VSP_020629
	Alternative sequence	238 – 253	16	Missing in isoform 3.		VSP_020630
	Natural variant	106	1	C → Y. Corresponds to variant rs34949802 [ dbSNP | Ensembl ].		VAR_049018
Experimental info
	Mutagenesis	204	1	Y → D: Mimics constitutively phosphorylated form and has the ability to interact with CD2AP and CIN85/SH3KBP1 without EGF treatment. Ref.2
	Mutagenesis	204	1	Y → F: Abolishes interaction with CD2AP and CIN85/SH3KBP1. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 7C765A0E96DC0F45	FASTA	273	28,783
	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
	Isoform 2 (Delta 5) [UniParc]. Checksum: E5E04F5CFBC399C4	FASTA	233	24,532
	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 VPGYLRIGKG GLLERTASRL GSRASTLRRN DSIYEASSLY GISAMDGVPF 190 200 210 220 230 TLHPRFEGKS CSPLAFSAFG DLTIKSLADI EEEYNYGFVV EKTAAARLPP SVS
	Isoform 3 (Delta 8) [UniParc]. Checksum: CE551F6F2AA734C9	FASTA	257	27,050
	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 CSPLAFSYNY 250 GFVVEKTAAA RLPPSVS

References

	« Hide 'large scale' referencesShow '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, 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.
IPI	IPI00744702. IPI00787031. IPI00788162.
RefSeq	NP_612410.1. NM_138401.2.
UniGene	Hs.515243.
3D structure databases
ProteinModelPortal	Q96EY5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96EY5. 1 interaction.
STRING	9606.ENSP00000324810.
PTM databases
PhosphoSite	Q96EY5.
Polymorphism databases
DMDM	74731632.
Proteomic databases
PaxDb	Q96EY5.
PRIDE	Q96EY5.
Protocols and materials databases
DNASU	93343.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317040; ENSP00000324810; ENSG00000141971. ENST00000392702; ENSP00000376466; ENSG00000141971. ENST00000543795; ENSP00000444653; ENSG00000141971.
GeneID	93343.
KEGG	hsa:93343.
UCSC	uc002ngo.1. human.
Organism-specific databases
CTD	93343.
GeneCards	GC19P017530.
HGNC	HGNC:25153. MVB12A.
HPA	HPA041885. HPA042231.
neXtProt	NX_Q96EY5.
PharmGKB	PA162385826.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG301965.
HOGENOM	HOG000231822.
HOVERGEN	HBG055538.
InParanoid	Q96EY5.
KO	K12186.
OMA	IYEASNL.
OrthoDB	EOG4BVRVC.
PhylomeDB	Q96EY5.
Gene expression databases
ArrayExpress	Q96EY5.
Bgee	Q96EY5.
CleanEx	HS_FAM125A.
Genevestigator	Q96EY5.
GermOnline	ENSG00000141971. Homo sapiens.
Family and domain databases
InterPro	IPR018798. FAM125. IPR023341. MABP. IPR023340. UMA. [Graphical view]
Pfam	PF10240. DUF2464. 1 hit. [Graphical view]
PROSITE	PS51498. MABP. 1 hit. PS51497. UMA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FAM125A. human.
GenomeRNAi	93343.
NextBio	78049.
PMAP-CutDB	Q96EY5.

Entry information

Entry name

MB12A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.