ID   CAH8_HUMAN              Reviewed;         290 AA.
AC   P35219; A8K0A5; B3KQZ7; Q32MY2;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   24-JAN-2024, entry version 187.
DE   RecName: Full=Carbonic anhydrase-related protein;
DE            Short=CARP;
DE   AltName: Full=Carbonic anhydrase VIII;
DE            Short=CA-VIII;
GN   Name=CA8; Synonyms=CALS;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8482548; DOI=10.1016/0378-1119(93)90385-g;
RA   Skaggs L.A., Bergenhem N.C.H., Venta P.J., Tashian R.E.;
RT   "The deduced amino acid sequence of human carbonic anhydrase-related
RT   protein (CARP) is 98% identical to the mouse homologue.";
RL   Gene 126:291-292(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Chen Y., Huang C.-H.;
RT   "Molecular identification of carbonic anhydrases (CA) and CA-related (CAR)
RT   genes.";
RL   Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cerebellum;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX   PubMed=19360879; DOI=10.1002/prot.22411;
RA   Picaud S.S., Muniz J.R.C., Kramm A., Pilka E.S., Kochan G., Oppermann U.,
RA   Yue W.W.;
RT   "Crystal structure of human carbonic anhydrase-related protein VIII reveals
RT   the basis for catalytic silencing.";
RL   Proteins 76:507-511(2009).
RN   [8]
RP   VARIANT CAMRQ3 PRO-100, AND CHARACTERIZATION OF VARIANT CAMRQ3 PRO-100.
RX   PubMed=19461874; DOI=10.1371/journal.pgen.1000487;
RA   Turkmen S., Guo G., Garshasbi M., Hoffmann K., Alshalah A.J., Mischung C.,
RA   Kuss A., Humphrey N., Mundlos S., Robinson P.N.;
RT   "CA8 mutations cause a novel syndrome characterized by ataxia and mild
RT   mental retardation with predisposition to quadrupedal gait.";
RL   PLoS Genet. 5:E1000487-E1000487(2009).
CC   -!- FUNCTION: Does not have a carbonic anhydrase catalytic activity.
CC   -!- INTERACTION:
CC       P35219; O43186: CRX; NbExp=7; IntAct=EBI-718700, EBI-748171;
CC       P35219; Q9UJY4: GGA2; NbExp=6; IntAct=EBI-718700, EBI-447646;
CC       P35219; Q9BPX1: HSD17B14; NbExp=14; IntAct=EBI-718700, EBI-742664;
CC       P35219; Q9NVH2: INTS7; NbExp=3; IntAct=EBI-718700, EBI-11276282;
CC       P35219; Q9P2G9-2: KLHL8; NbExp=3; IntAct=EBI-718700, EBI-11959635;
CC       P35219; Q03252: LMNB2; NbExp=3; IntAct=EBI-718700, EBI-2830427;
CC       P35219; Q8TBB1: LNX1; NbExp=6; IntAct=EBI-718700, EBI-739832;
CC       P35219; Q9Y5V3: MAGED1; NbExp=9; IntAct=EBI-718700, EBI-716006;
CC       P35219; Q9BZG1: RAB34; NbExp=3; IntAct=EBI-718700, EBI-2856739;
CC       P35219; Q96EA4: SPDL1; NbExp=6; IntAct=EBI-718700, EBI-715381;
CC       P35219; O15119: TBX3; NbExp=3; IntAct=EBI-718700, EBI-3452216;
CC   -!- DISEASE: Cerebellar ataxia, impaired intellectual development, and
CC       dysequilibrium syndrome 3 (CAMRQ3) [MIM:613227]: An autosomal
CC       recessive, congenital cerebellar ataxia associated with dysarthia,
CC       quadrupedal gait and intellectual disability.
CC       {ECO:0000269|PubMed:19461874}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC       {ECO:0000305}.
CC   -!- CAUTION: Although it belongs to the alpha-carbonic anhydrase family,
CC       Arg-116 is present instead of the conserved His which is a zinc-binding
CC       residue. It is therefore expected that this protein lacks carbonic
CC       anhydrase activity. {ECO:0000305}.
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DR   EMBL; L04656; AAA35653.2; -; mRNA.
DR   EMBL; AY075022; AAL78170.1; -; mRNA.
DR   EMBL; AK289470; BAF82159.1; -; mRNA.
DR   EMBL; AK314538; BAG37128.1; -; mRNA.
DR   EMBL; AK090655; BAG52209.1; -; mRNA.
DR   EMBL; CH471068; EAW86826.1; -; Genomic_DNA.
DR   EMBL; BC069744; AAH69744.1; -; mRNA.
DR   EMBL; BC069794; AAH69794.1; -; mRNA.
DR   EMBL; BC108929; AAI08930.1; -; mRNA.
DR   CCDS; CCDS6174.1; -.
DR   PIR; JN0576; JN0576.
DR   RefSeq; NP_001308766.1; NM_001321837.1.
DR   RefSeq; NP_001308767.1; NM_001321838.1.
DR   RefSeq; NP_001308768.1; NM_001321839.1.
DR   RefSeq; NP_004047.3; NM_004056.5.
DR   PDB; 2W2J; X-ray; 1.60 A; A=1-290.
DR   PDBsum; 2W2J; -.
DR   AlphaFoldDB; P35219; -.
DR   SMR; P35219; -.
DR   BioGRID; 107222; 39.
DR   IntAct; P35219; 35.
DR   MINT; P35219; -.
DR   STRING; 9606.ENSP00000314407; -.
DR   DrugBank; DB00909; Zonisamide.
DR   GlyGen; P35219; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P35219; -.
DR   PhosphoSitePlus; P35219; -.
DR   BioMuta; CA8; -.
DR   DMDM; 461681; -.
DR   EPD; P35219; -.
DR   jPOST; P35219; -.
DR   MassIVE; P35219; -.
DR   MaxQB; P35219; -.
DR   PaxDb; 9606-ENSP00000314407; -.
DR   PeptideAtlas; P35219; -.
DR   ProteomicsDB; 54985; -.
DR   Pumba; P35219; -.
DR   Antibodypedia; 11840; 330 antibodies from 35 providers.
DR   CPTC; P35219; 2 antibodies.
DR   DNASU; 767; -.
DR   Ensembl; ENST00000317995.5; ENSP00000314407.4; ENSG00000178538.10.
DR   GeneID; 767; -.
DR   KEGG; hsa:767; -.
DR   MANE-Select; ENST00000317995.5; ENSP00000314407.4; NM_004056.6; NP_004047.3.
DR   UCSC; uc003xtz.2; human.
DR   AGR; HGNC:1382; -.
DR   CTD; 767; -.
DR   DisGeNET; 767; -.
DR   GeneCards; CA8; -.
DR   HGNC; HGNC:1382; CA8.
DR   HPA; ENSG00000178538; Tissue enhanced (brain, parathyroid gland).
DR   MalaCards; CA8; -.
DR   MIM; 114815; gene.
DR   MIM; 613227; phenotype.
DR   neXtProt; NX_P35219; -.
DR   OpenTargets; ENSG00000178538; -.
DR   Orphanet; 1766; Dysequilibrium syndrome.
DR   PharmGKB; PA25997; -.
DR   VEuPathDB; HostDB:ENSG00000178538; -.
DR   eggNOG; KOG0382; Eukaryota.
DR   GeneTree; ENSGT00940000158863; -.
DR   HOGENOM; CLU_039326_2_1_1; -.
DR   InParanoid; P35219; -.
DR   OMA; SANGEYQ; -.
DR   OrthoDB; 49814at2759; -.
DR   PhylomeDB; P35219; -.
DR   TreeFam; TF316425; -.
DR   BRENDA; 4.2.1.1; 2681.
DR   PathwayCommons; P35219; -.
DR   SignaLink; P35219; -.
DR   BioGRID-ORCS; 767; 14 hits in 1158 CRISPR screens.
DR   ChiTaRS; CA8; human.
DR   EvolutionaryTrace; P35219; -.
DR   GeneWiki; CA8; -.
DR   GenomeRNAi; 767; -.
DR   Pharos; P35219; Tbio.
DR   PRO; PR:P35219; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; P35219; Protein.
DR   Bgee; ENSG00000178538; Expressed in metanephros cortex and 118 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR   GO; GO:0016836; F:hydro-lyase activity; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
DR   GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl.
DR   CDD; cd03120; alpha_CARP_VIII; 1.
DR   Gene3D; 3.10.200.10; Alpha carbonic anhydrase; 1.
DR   InterPro; IPR001148; CA_dom.
DR   InterPro; IPR036398; CA_dom_sf.
DR   InterPro; IPR023561; Carbonic_anhydrase_a-class.
DR   InterPro; IPR018338; Carbonic_anhydrase_a-class_CS.
DR   InterPro; IPR041877; CARP_VIII.
DR   PANTHER; PTHR18952; CARBONIC ANHYDRASE; 1.
DR   PANTHER; PTHR18952:SF104; CARBONIC ANHYDRASE-RELATED PROTEIN; 1.
DR   Pfam; PF00194; Carb_anhydrase; 1.
DR   SMART; SM01057; Carb_anhydrase; 1.
DR   SUPFAM; SSF51069; Carbonic anhydrase; 1.
DR   PROSITE; PS00162; ALPHA_CA_1; 1.
DR   PROSITE; PS51144; ALPHA_CA_2; 1.
DR   Genevisible; P35219; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Disease variant; Intellectual disability; Metal-binding;
KW   Phosphoprotein; Reference proteome; Zinc.
FT   CHAIN           1..290
FT                   /note="Carbonic anhydrase-related protein"
FT                   /id="PRO_0000077433"
FT   DOMAIN          27..289
FT                   /note="Alpha-carbonic anhydrase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT   REGION          1..26
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        87
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         118
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255"
FT   BINDING         141
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255"
FT   SITE            116
FT                   /note="Ancestral zinc ligand"
FT   MOD_RES         5
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5PPN4"
FT   VARIANT         100
FT                   /note="S -> P (in CAMRQ3; affects protein stability owing
FT                   to accelerated proteasomal degradation; dbSNP:rs267606695)"
FT                   /evidence="ECO:0000269|PubMed:19461874"
FT                   /id="VAR_063634"
FT   CONFLICT        106
FT                   /note="Q -> R (in Ref. 3; BAG52209)"
FT                   /evidence="ECO:0000305"
FT   STRAND          31..34
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           37..39
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           42..45
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           56..58
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           63..66
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          71..73
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          77..84
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          89..92
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          97..101
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          110..119
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          128..131
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          137..146
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   TURN            147..149
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           153..156
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          163..174
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           177..183
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           184..189
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          194..199
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           203..206
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          215..221
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          229..238
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          240..242
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           244..250
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          254..256
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   STRAND          286..288
FT                   /evidence="ECO:0007829|PDB:2W2J"
SQ   SEQUENCE   290 AA;  32973 MW;  C142711660A972DB CRC64;
     MADLSFIEDT VAFPEKEEDE EEEEEGVEWG YEEGVEWGLV FPDANGEYQS PINLNSREAR
     YDPSLLDVRL SPNYVVCRDC EVTNDGHTIQ VILKSKSVLS GGPLPQGHEF ELYEVRFHWG
     RENQRGSEHT VNFKAFPMEL HLIHWNSTLF GSIDEAVGKP HGIAIIALFV QIGKEHVGLK
     AVTEILQDIQ YKGKSKTIPC FNPNTLLPDP LLRDYWVYEG SLTIPPCSEG VTWILFRYPL
     TISQLQIEEF RRLRTHVKGA ELVEGCDGIL GDNFRPTQPL SDRVIRAAFQ
//