Q9Y4U1 (MMAC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methylmalonic aciduria and homocystinuria type C protein

Gene names

Name:

MMACHC

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	282 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12).
Pathway	Cofactor biosynthesis; adenosylcobalamin biosynthesis.
Tissue specificity	Widely expressed. Expressed at higher level in fetal liver. Also expressed in spleen, lymph node, thymus and bone marrow. Weakly or not expressed in peripheral blood leukocytes. Ref.8
Involvement in disease	Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400]: A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the MMACHC family.
Sequence caution	The sequence AAH06122.3 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Disease	Disease mutation
Ligand	Cobalamin Cobalt
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cobalamin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	cobalamin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 282

282

Methylmalonic aciduria and homocystinuria type C protein

PRO_0000076258

Amino acid modifications

Modified residue

245

1

Phosphoserine Ref.4

Modified residue

247

1

Phosphoserine Ref.6

Modified residue

275

1

Phosphoserine Ref.5 Ref.6

Modified residue

279

1

Phosphoserine Ref.6

Natural variations

Natural variant

27

1

Q → R in MMAHCC. Ref.8

VAR_024770

Natural variant

116

1

L → P in MMAHCC. Ref.8

VAR_024771

Natural variant

122

1

H → R in MMAHCC. Ref.8

VAR_024772

Natural variant

130

1

Y → H in MMAHCC. Ref.8

VAR_024773

Natural variant

147

1

G → A in MMAHCC. Ref.8

VAR_024774

Natural variant

147

1

G → D in MMAHCC. Ref.8

VAR_024775

Natural variant

156

1

G → D in MMAHCC. Ref.8

VAR_024776

Natural variant

157

1

W → C in MMAHCC. Ref.8

VAR_024777

Natural variant

161

1

R → G in MMAHCC. Ref.8

VAR_024778

Natural variant

161

1

R → Q in MMAHCC. Ref.8

VAR_024779

Natural variant

189

1

R → S in MMAHCC. Ref.8

VAR_024780

Natural variant

193

1

L → P in MMAHCC. Ref.8

VAR_024781

Natural variant

206

1

R → P in MMAHCC. Ref.8

VAR_024782

Natural variant

206

1

R → W in MMAHCC. Ref.8

VAR_024783

Natural variant

271

1

S → G.
Corresponds to variant rs35219601 [ dbSNP | Ensembl ].

VAR_038805

Experimental info

Sequence conflict

100

1

E → G in CAB45693. Ref.1

Secondary structure

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282

Helix Strand Turn

Details...

Helix

3 – 16

14

Helix

17 – 19

3

Beta strand

21 – 27

7

Helix

28 – 32

5

Helix

37 – 39

3

Beta strand

47 – 54

8

Helix

58 – 61

4

Helix

63 – 66

4

Beta strand

74 – 76

3

Helix

78 – 93

16

Beta strand

100 – 103

4

Helix

104 – 106

3

Beta strand

113 – 115

3

Helix

117 – 123

7

Beta strand

126 – 130

5

Helix

132 – 134

3

Beta strand

135 – 137

3

Beta strand

148 – 151

4

Turn

152 – 154

3

Beta strand

159 – 170

12

Helix

186 – 198

13

Helix

200 – 202

3

Helix

204 – 207

4

Helix

217 – 222

6

Helix

226 – 229

4

Turn

235 – 237

3

Sequences

	Sequence		Length	Mass (Da)
	Q9Y4U1 [UniParc]. Last modified January 10, 2006. Version 3. Checksum: 3A7E6BC774CB5D17	FASTA	282	31,728
	10 20 30 40 50 60 MEPKVAELKQ KIEDTLCPFG FEVYPFQVAW YNELLPPAFH LPLPGPTLAF LVLSTPAMFD 70 80 90 100 110 120 RALKPFLQSC HLRMLTDPVD QCVAYHLGRV RESLPELQIE IIADYEVHPN RRPKILAQTA 130 140 150 160 170 180 AHVAGAAYYY QRQDVEADPW GNQRISGVCI HPRFGGWFAI RGVVLLPGIE VPDLPPRKPH 190 200 210 220 230 240 DCVPTRADRI ALLEGFNFHW RDWTYRDAVT PQERYSEEQK AYFSTPPAQR LALLGLAQPS 250 260 270 280 EKPSSPSPDL PFTTPAPKKP GNPSRARSWL SPRVSPPASP GP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] OF 4-282. Tissue: Lung.
[4]	"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-245, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[5]	"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-275, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[6]	"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-247; SER-275 AND SER-279, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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].
[8]	"Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type." Lerner-Ellis J.P., Tirone J.C., Pawelek P.D., Dore C., Atkinson J.L., Watkins D., Morel C.F., Fujiwara T.M., Moras E., Hosack A.R., Dunbar G.V., Antonicka H., Forgetta V., Dobson C.M., Leclerc D., Gravel R.A., Shoubridge E.A., Coulton J.W. , Lepage P., Rommens J.M., Morgan K., Rosenblatt D.S. Nat. Genet. 38:93-100(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MMAHCC ARG-27; PRO-116; ARG-122; HIS-130; ASP-147; ALA-147; ASP-156; CYS-157; GLY-161; GLN-161; SER-189; PRO-193; TRP-206 AND PRO-206, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AL080062 mRNA. Translation: CAB45693.2.
AL451136 Genomic DNA. Translation: CAI13094.1.
BC006122 mRNA. Translation: AAH06122.3. Different initiation.

IPI

IPI00001053.

PIR

T12462.

RefSeq

NP_056321.2. NM_015506.2.

UniGene

Hs.13024.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3SBY	X-ray	2.71	A/B	1-244	[»]
3SBZ	X-ray	2.00	A	1-244	[»]
3SC0	X-ray	1.95	A	1-238	[»]
3SOM	X-ray	2.40	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P	1-282	[»]

ProteinModelPortal

Q9Y4U1.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000361154.

PTM databases

PhosphoSite

Q9Y4U1.

Polymorphism databases

DMDM

85681045.

Proteomic databases

PaxDb

Q9Y4U1.

PRIDE

Q9Y4U1.

Protocols and materials databases

DNASU

25974.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000401061; ENSP00000383840; ENSG00000132763.

GeneID

25974.

KEGG

hsa:25974.

UCSC

uc009vxv.3. human.

Organism-specific databases

CTD

25974.

GeneCards

GC01P045965.

H-InvDB

HIX0000532.

HGNC

HGNC:24525. MMACHC.

HPA

HPA027394.
HPA027399.
HPA027402.

MIM

277400. phenotype.
603174. phenotype.
609831. gene.

neXtProt

NX_Q9Y4U1.

Orphanet

79282. Methylmalonic acidemia with homocystinuria, type cblC.

PharmGKB

PA142671348.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG80998.

HOGENOM

HOG000231413.

HOVERGEN

HBG080267.

InParanoid

Q9Y4U1.

KO

K14618.

OMA

FQVAWYN.

OrthoDB

EOG4F7NKW.

Enzyme and pathway databases

UniPathway

UPA00148.

Gene expression databases

Bgee

Q9Y4U1.

CleanEx

HS_MMACHC.

Genevestigator

Q9Y4U1.

GermOnline

ENSG00000132763. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other

ChiTaRS

MMACHC. human.

DrugBank

DB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

EvolutionaryTrace

Q9Y4U1.

GenomeRNAi

25974.

NextBio

47614.

SOURCE

Search...

Entry information

Entry name

MMAC_HUMAN

Accession

Primary (citable) accession number: Q9Y4U1
Secondary accession number(s): Q5T157, Q9BRQ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	January 10, 2006
Last modified:	May 1, 2013
This is version 88 of the entry and version 3 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.