Q9HCJ1 (ANKH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Progressive ankylosis protein homolog
Short name=ANK

Gene names

Name:	ANKH
Synonyms:	KIAA1581
ORF Names:	UNQ241/PRO274

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

General annotation (Comments)

Function	Regulates intra- and extracellular levels of inorganic pyrophosphate (PPi), probably functioning as PPi transporter.
Subcellular location	Membrane; Multi-pass membrane protein Probable.
Tissue specificity	Found in osteoblasts from mandibular bone and from iliac bone; not detected in osteoclastic cells.
Involvement in disease	Chondrocalcinosis 2 (CCAL2) [MIM:118600]: Chondrocalcinosis is a common cause of joint pain and arthritis caused by calcium deposition in articular cartilage and the presence of calcium hypophosphate crystals in synovial fluid, cartilage and periarticular soft tissue.DEAL2 inheritance is autosomal dominant. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11 Craniometaphyseal dysplasia Jackson type (CMDJ) [MIM:123000]: Rare autosomal dominant skeletal disorder characterized by abnormal bone formation and mineralization in membranous as well as endochondral bones. Progressive thickening of the bones can cause narrowing of cranial foramina and can lead to severe visual and neurological impairment, such as facial palsy and deafness. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8
Sequence similarities	Belongs to the ANKH family.
Sequence caution	The sequence BAB13407.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Phosphate transport Transport
Cellular component	Membrane
Disease	Deafness Disease mutation
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	locomotory behavior Non-traceable author statement Ref.1. Source: UniProtKB regulation of bone mineralization Inferred from sequence or structural similarity. Source: UniProtKB skeletal system development Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB outer membrane Traceable author statement Ref.8. Source: UniProtKB
Molecular_function	inorganic diphosphate transmembrane transporter activity Inferred from direct assay Ref.8. Source: UniProtKB inorganic phosphate transmembrane transporter activity Inferred from direct assay Ref.8. Source: UniProtKB phosphate ion transmembrane transporter 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
	Chain	1 – 492	492	Progressive ankylosis protein homolog		PRO_0000137467
Regions
	Topological domain	1 – 85	85	Cytoplasmic Potential
	Transmembrane	86 – 106	21	Helical; Potential
	Topological domain	107 – 131	25	Extracellular Potential
	Transmembrane	132 – 152	21	Helical; Potential
	Topological domain	153 – 158	6	Cytoplasmic Potential
	Transmembrane	159 – 179	21	Helical; Potential
	Topological domain	180 – 189	10	Extracellular Potential
	Transmembrane	190 – 210	21	Helical; Potential
	Topological domain	211 – 326	116	Cytoplasmic Potential
	Transmembrane	327 – 347	21	Helical; Potential
	Topological domain	348 – 350	3	Extracellular Potential
	Transmembrane	351 – 371	21	Helical; Potential
	Topological domain	372 – 403	32	Cytoplasmic Potential
	Transmembrane	404 – 426	23	Helical; Potential
	Topological domain	427 – 429	3	Extracellular Potential
	Transmembrane	430 – 452	23	Helical; Potential
	Topological domain	453 – 492	40	Cytoplasmic Potential
Natural variations
	Natural variant	5	1	P → L in CCAL2. Ref.10		VAR_022606
	Natural variant	5	1	P → T in CCAL2. Ref.11		VAR_022607
	Natural variant	48	1	M → T in CCAL2. Ref.9		VAR_017556
	Natural variant	292	1	W → R in CMDJ. Ref.8		VAR_012192
	Natural variant	331	1	C → R in CMDJ. Ref.8		VAR_012193
	Natural variant	375	1	Missing in CMDJ. Ref.7 Ref.8		VAR_012194
	Natural variant	376	1	Missing in CMDJ. Ref.7		VAR_012195
	Natural variant	377	1	Missing in CMDJ. Ref.8		VAR_012196
	Natural variant	380	1	P → PA in CMDJ. Ref.7 Ref.8		VAR_012197
	Natural variant	389	1	G → R in CMDJ. Ref.8 Corresponds to variant rs28939080 [ dbSNP | Ensembl ].		VAR_012198
	Natural variant	490	1	Missing in CCAL2; sporadic. Ref.9		VAR_017557
Experimental info
	Sequence conflict	78	1	N → S in AAF88039. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9HCJ1 [UniParc]. Last modified November 16, 2001. Version 2. Checksum: 44BFEE9089BDEC6B	FASTA	492	54,241
	10 20 30 40 50 60 MVKFPALTHY WPLIRFLVPL GITNIAIDFG EQALNRGIAA VKEDAVEMLA SYGLAYSLMK 70 80 90 100 110 120 FFTGPMSDFK NVGLVFVNSK RDRTKAVLCM VVAGAIAAVF HTLIAYSDLG YYIINKLHHV 130 140 150 160 170 180 DESVGSKTRR AFLYLAAFPF MDAMAWTHAG ILLKHKYSFL VGCASISDVI AQVVFVAILL 190 200 210 220 230 240 HSHLECREPL LIPILSLYMG ALVRCTTLCL GYYKNIHDII PDRSGPELGG DATIRKMLSF 250 260 270 280 290 300 WWPLALILAT QRISRPIVNL FVSRDLGGSS AATEAVAILT ATYPVGHMPY GWLTEIRAVY 310 320 330 340 350 360 PAFDKNNPSN KLVSTSNTVT AAHIKKFTFV CMALSLTLCF VMFWTPNVSE KILIDIIGVD 370 380 390 400 410 420 FAFAELCVVP LRIFSFFPVP VTVRAHLTGW LMTLKKTFVL APSSVLRIIV LIASLVVLPY 430 440 450 460 470 480 LGVHGATLGV GSLLAGFVGE STMVAIAACY VYRKQKKKME NESATEGEDS AMTDMPPTEE 490 VTDIVEMREE NE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Role of the mouse ank gene in control of tissue calcification and arthritis." Ho A.M., Johnson M.D., Kingsley D.M. Science 289:265-270(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O. DNA Res. 7:273-281(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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.
[5]	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].
[6]	"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]. Tissue: Ovary.
[7]	"Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK." Reichenberger E., Tiziani V., Watanabe S., Park L., Ueki Y., Santanna C., Baur S.T., Shiang R., Grange D.K., Beighton P., Gardner J., Hamersma H., Sellars S., Ramesar R., Lidral A.C., Sommer A., Raposo do Amaral C.M., Gorlin R.J., Mulliken J.B., Olsen B.R. Am. J. Hum. Genet. 68:1321-1326(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CMDJ SER-375 DEL; PHE-376 DEL AND ALA-380 INS.
[8]	"Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia." Nuernberg P., Thiele H., Chandler D., Hoehne W., Cunningham M.L., Ritter H., Leschik G., Uhlmann K., Mischung C., Harrop K., Goldblatt J., Borochowitz Z.U., Kotzot D., Westermann F., Mundlos S., Braun H.-S., Laing N., Tinschert S. Nat. Genet. 28:37-41(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CMDJ ARG-292; ARG-331; SER-375 DEL; PHE-377 DEL; ALA-380 INS AND ARG-389.
[9]	"Mutations in ANKH cause chondrocalcinosis." Pendleton A., Johnson M.D., Hughes A., Gurley K.A., Ho A.M., Doherty M., Dixey J., Gillet P., Loeuille D., McGrath R., Reginato A., Shiang R., Wright G., Netter P., Williams C., Kingsley D.M. Am. J. Hum. Genet. 71:933-940(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCAL2 THR-48 AND GLU-490 DEL.
[10]	"Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH." Williams C.J., Zhang Y., Timms A., Bonavita G., Caeiro F., Broxholme J., Cuthbertson J., Jones Y., Marchegiani R., Reginato A., Russell R.G.G., Wordsworth B.P., Carr A.J., Brown M.A. Am. J. Hum. Genet. 71:985-991(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCAL2 LEU-5.
[11]	"Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease." Williams C.J., Pendleton A., Bonavita G., Reginato A.J., Hughes A.E., Peariso S., Doherty M., McCarty D.J., Ryan L.M. Arthritis Rheum. 48:2627-2631(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCAL2 THR-5.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF274753 mRNA. Translation: AAF88039.1. AB046801 mRNA. Translation: BAB13407.1. Different initiation. AY358503 mRNA. Translation: AAQ88867.1. AK315012 mRNA. Translation: BAG37504.1. CH471102 Genomic DNA. Translation: EAX08034.1. CH471102 Genomic DNA. Translation: EAX08035.1. BC009835 mRNA. Translation: AAH09835.1. BC014526 mRNA. Translation: AAH14526.1.
IPI	IPI00215869.
RefSeq	NP_473368.1. NM_054027.4.
UniGene	Hs.156727.
3D structure databases
ProteinModelPortal	Q9HCJ1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HCJ1. 1 interaction.
STRING	9606.ENSP00000284268.
Protein family/group databases
TCDB	2.A.66.9.1. multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) flippase superfamily.
PTM databases
PhosphoSite	Q9HCJ1.
Polymorphism databases
DMDM	17366849.
Proteomic databases
PaxDb	Q9HCJ1.
PRIDE	Q9HCJ1.
Protocols and materials databases
DNASU	56172.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000284268; ENSP00000284268; ENSG00000154122.
GeneID	56172.
KEGG	hsa:56172.
UCSC	uc003jfm.4. human.
Organism-specific databases
CTD	56172.
GeneCards	GC05M014706.
HGNC	HGNC:15492. ANKH.
MIM	118600. phenotype. 123000. phenotype. 605145. gene.
neXtProt	NX_Q9HCJ1.
Orphanet	1522. Craniometaphyseal dysplasia. 1416. Familial articular chondrocalcinosis.
PharmGKB	PA24801.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG19764.
HOGENOM	HOG000033943.
HOVERGEN	HBG018728.
InParanoid	Q9HCJ1.
OMA	YMGVHGA.
OrthoDB	EOG4MCX04.
PhylomeDB	Q9HCJ1.
Gene expression databases
ArrayExpress	Q9HCJ1.
Bgee	Q9HCJ1.
CleanEx	HS_ANKH.
Genevestigator	Q9HCJ1.
GermOnline	ENSG00000154122. Homo sapiens.
Family and domain databases
InterPro	IPR009887. ANKH. [Graphical view]
Pfam	PF07260. ANKH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ANKH. human.
GenomeRNAi	56172.
NextBio	61818.
SOURCE	Search...

Entry information

Entry name

ANKH_HUMAN

Accession

Primary (citable) accession number: Q9HCJ1
Secondary accession number(s): B2RCA7, D3DTD4, Q9NQW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	November 16, 2001
Last modified:	May 1, 2013
This is version 105 of the entry and version 2 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.