CA4

Protein identityUniProt · HPA

UniProt accession

P22748

Gene

CA4

Ensembl

ENSG00000167434

Chromosome

17

Canonical length

312 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Vesicles,Cytosol

OverviewNCBI Gene

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This gene encodes a glycosylphosphatidyl-inositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and proximal renal tubules. Its exact function is not known; however, it may have a role in inherited renal abnormalities of bicarbonate transport. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

312 residues, UniProt reviewed canonical sequence.

>P22748|CA4
     1  MRMLLALLAL SAARPSASAE SHWCYEVQAE SSNYPCLVPV KWGGNCQKDR QSPINIVTTK
    61  AKVDKKLGRF FFSGYDKKQT WTVQNNGHSV MMLLENKASI SGGGLPAPYQ AKQLHLHWSD
   121  LPYKGSEHSL DGEHFAMEMH IVHEKEKGTS RNVKEAQDPE DEIAVLAFLV EAGTQVNEGF
   181  QPLVEALSNI PKPEMSTTMA ESSLLDLLPK EEKLRHYFRY LGSLTTPTCD EKVVWTVFRE
   241  PIQLHREQIL AFSQKLYYDK EQTVSMKDNV RPLQQLGQRT VIKSGAPGRP LPWALPALLG
   301  PMLACLLAGF LR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

247 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CA4.

Disease | AllUniProt

Conditions CA4 is implicated in, by any mechanism.

• Retinitis pigmentosa 17 (RP17) MIM:600852

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 350 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Retinal dystrophy

ReferencesPubMed · IEDB

Publications for CA4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.15

gnomAD pLI

0

gnomAD missense Z

-0.12

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bicarbonate transport

Molecular functions

• carbonate dehydratase activity
• zinc ion binding

Cellular components

• apical plasma membrane
• brush border membrane
• cell surface
• endoplasmic reticulum-Golgi intermediate compartment
• external side of plasma membrane
• extracellular exosome
• Golgi apparatus
• membrane
• perinuclear region of cytoplasm
• plasma membrane
• rough endoplasmic reticulum
• secretory granule membrane
• trans-Golgi network
• transport vesicle membrane

Protein domainsUniProt · Pfam · InterPro

• Alpha carbonic anhydrase domain
• Carbonic anhydrase, alpha-class, conserved site
• Carbonic anhydrase, alpha-class
• Alpha carbonic anhydrase domain superfamily
• Eukaryotic-type carbonic anhydrase
• Carbonic anhydrase, CA4/CA15

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• GPI-anchor
• Lipoprotein
• Lyase
• Membrane
• Metal-binding
• Retinitis pigmentosa
• Signal
• Zinc

InteractionsUniProt · HPA

Protein binding partners of CA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SLC4A4