Q8IVH4 (MMAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methylmalonic aciduria type A protein, mitochondrial
EC=3.6.-.-

Gene names

Name:

MMAA

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	418 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable GTPase. May function as chaperone. May be involved in the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis.
Pathway	Cofactor biosynthesis; adenosylcobalamin biosynthesis.
Subunit structure	Homodimer. Ref.5
Subcellular location	Mitochondrion Probable.
Tissue specificity	Widely expressed. Highest expression is observed in liver and skeletal muscle.
Involvement in disease	Methylmalonic aciduria type cblA (MMAA) [MIM:251100]: A disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.6 Ref.7
Sequence similarities	Belongs to the ArgK family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	GTP-binding Nucleotide-binding
Molecular function	Chaperone Hydrolase
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: UniProtKB-SubCell
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 65

65

Mitochondrion Potential

Chain

66 – 418

353

Methylmalonic aciduria type A protein, mitochondrial

PRO_0000002285

Regions

Nucleotide binding

150 – 158

9

GTP

Nucleotide binding

328 – 330

3

GTP

Sites

Binding site

292

1

GTP

Natural variations

Natural variant

89

1

L → P in MMAA. Ref.6

VAR_020835

Natural variant

145

1

R → Q in MMAA. Ref.6

VAR_020836

Natural variant

207

1

Y → C in MMAA. Ref.1 Ref.6

VAR_017202

Natural variant

218

1

G → E in MMAA. Ref.6

VAR_020837

Natural variant

359

1

R → G in MMAA. Ref.7

VAR_038804

Natural variant

359

1

R → Q in MMAA. Ref.6

VAR_020838

Natural variant

363

1

Q → H. Ref.6
Corresponds to variant rs2270655 [ dbSNP | Ensembl ].

VAR_020423

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

418

Helix Strand Turn

Details...

Helix

80 – 94

15

Helix

98 – 109

12

Helix

113 – 135

23

Turn

136 – 139

4

Beta strand

144 – 149

6

Helix

156 – 169

14

Beta strand

174 – 178

5

Beta strand

206 – 209

4

Helix

224 – 233

10

Beta strand

237 – 242

6

Helix

250 – 254

5

Beta strand

258 – 264

7

Beta strand

284 – 288

5

Helix

293 – 295

3

Helix

296 – 310

15

Beta strand

323 – 326

4

Turn

329 – 331

3

Helix

335 – 352

18

Helix

354 – 381

28

Helix

383 – 397

15

Helix

403 – 415

13

Sequences

	Sequence		Length	Mass (Da)
	Q8IVH4 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: AD9EA19DDB8DEEF8	FASTA	418	46,538
	10 20 30 40 50 60 MPMLLPHPHQ HFLKGLLRAP FRCYHFIFHS STHLGSGIPC AQPFNSLGLH CTKWMLLSDG 70 80 90 100 110 120 LKRKLCVQTT LKDHTEGLSD KEQRFVDKLY TGLIQGQRAC LAEAITLVES THSRKKELAQ 130 140 150 160 170 180 VLLQKVLLYH REQEQSNKGK PLAFRVGLSG PPGAGKSTFI EYFGKMLTER GHKLSVLAVD 190 200 210 220 230 240 PSSCTSGGSL LGDKTRMTEL SRDMNAYIRP SPTRGTLGGV TRTTNEAILL CEGAGYDIIL 250 260 270 280 290 300 IETVGVGQSE FAVADMVDMF VLLLPPAGGD ELQGIKRGII EMADLVAVTK SDGDLIVPAR 310 320 330 340 350 360 RIQAEYVSAL KLLRKRSQVW KPKVIRISAR SGEGISEMWD KMKDFQDLML ASGELTAKRR 370 380 390 400 410 KQQKVWMWNL IQESVLEHFR THPTVREQIP LLEQKVLIGA LSPGLAADFL LKAFKSRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements." Dobson C.M., Wai T., Leclerc D., Wilson A., Wu X., Dore C., Hudson T., Rosenblatt D.S., Gravel R.A. Proc. Natl. Acad. Sci. U.S.A. 99:15554-15559(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MMAA CYS-207.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation." Froese D.S., Kochan G., Muniz J.R., Wu X., Gileadi C., Ugochukwu E., Krysztofinska E., Gravel R.A., Oppermann U., Yue W.W. J. Biol. Chem. 285:38204-38213(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 72-418 IN COMPLEX WITH GDP, SUBUNIT.
[6]	"Mutations in the MMAA gene in patients with the cblA disorder of vitamin B(12) metabolism." Lerner-Ellis J.P., Dobson C.M., Wai T., Watkins D., Tirone J.C., Leclerc D., Dore C., Lepage P., Gravel R.A., Rosenblatt D.S. Hum. Mutat. 24:509-516(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MMAA PRO-89; GLN-145; CYS-207; GLU-218 AND GLN-359, VARIANT HIS-363.
[7]	"Mutation analysis of the MMAA and MMAB genes in Japanese patients with vitamin B(12)-responsive methylmalonic acidemia: identification of a prevalent MMAA mutation." Yang X., Sakamoto O., Matsubara Y., Kure S., Suzuki Y., Aoki Y., Suzuki Y., Sakura N., Takayanagi M., Iinuma K., Ohura T. Mol. Genet. Metab. 82:329-333(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MMAA GLY-359.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF524846 , AF524841, AF524842, AF524843, AF524844, AF524845 Genomic DNA. Translation: AAN77287.1.
AK126662 mRNA. Translation: BAG54352.1.
CH471056 Genomic DNA. Translation: EAX05036.1.
BC101178 mRNA. Translation: AAI01179.1.
BC101179 mRNA. Translation: AAI01180.1.

IPI

IPI01012901.

RefSeq

NP_758454.1. NM_172250.2.

UniGene

Hs.452864.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WWW	X-ray	2.64	A/B/C/D	72-418	[»]

ProteinModelPortal

Q8IVH4.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000281317.

PTM databases

PhosphoSite

Q8IVH4.

Polymorphism databases

DMDM

38258173.

Proteomic databases

PaxDb

Q8IVH4.

PRIDE

Q8IVH4.

Protocols and materials databases

DNASU

166785.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000281317; ENSP00000281317; ENSG00000151611.

GeneID

166785.

KEGG

hsa:166785.

UCSC

uc003ikh.4. human.

Organism-specific databases

CTD

166785.

GeneCards

GC04P146540.

HGNC

HGNC:18871. MMAA.

HPA

HPA037361.

MIM

251100. phenotype.
607481. gene.

neXtProt

NX_Q8IVH4.

Orphanet

79310. Vitamin B12-responsive methylmalonic acidemia type cblA.

PharmGKB

PA134912808.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1703.

HOVERGEN

HBG045588.

InParanoid

Q8IVH4.

KO

K07588.

OrthoDB

EOG49W2FR.

PhylomeDB

Q8IVH4.

Enzyme and pathway databases

UniPathway

UPA00148.

Gene expression databases

ArrayExpress

Q8IVH4.

Bgee

Q8IVH4.

CleanEx

HS_MMAA.

Genevestigator

Q8IVH4.

GermOnline

ENSG00000151611. Homo sapiens.

Family and domain databases

InterPro

IPR003593. AAA+_ATPase.
IPR005129. ArgK.
[Graphical view]

Pfam

PF03308. ArgK. 1 hit.
[Graphical view]

SMART

SM00382. AAA. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00750. lao. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

EvolutionaryTrace

Q8IVH4.

GenomeRNAi

166785.

NextBio

88619.

SOURCE

Search...

Entry information

Entry name

MMAA_HUMAN

Accession

Primary (citable) accession number: Q8IVH4
Secondary accession number(s): B3KX40, Q495G7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 92 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.