Seroatlas · Human Serome Atlas

ITIH4

Inter-alpha-trypsin inhibitor heavy chain H4

Also known as: H4P, IHRP, ITIH4_HUMAN, ITIHL1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q14624
Gene: ITIH4
Ensembl: ENSG00000055955
Chromosome: 3
Canonical length: 930 aa
Protein class: Cancer-related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
Subcellular location: Vesicles
Secretome location: Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

930 residues, UniProt reviewed canonical sequence.

>Q14624|ITIH4
     1  MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR
    61  ANTVQEATFQ MELPKKAFIT NFSMIIDGMT YPGIIKEKAE AQAQYSAAVA KGKSAGLVKA
   121  TGRNMEQFQV SVSVAPNAKI TFELVYEELL KRRLGVYELL LKVRPQQLVK HLQMDIHIFE
   181  PQGISFLETE STFMTNQLVD ALTTWQNKTK AHIRFKPTLS QQQKSPEQQE TVLDGNLIIR
   241  YDVDRAISGG SIQIENGYFV HYFAPEGLTT MPKNVVFVID KSGSMSGRKI QQTREALIKI
   301  LDDLSPRDQF NLIVFSTEAT QWRPSLVPAS AENVNKARSF AAGIQALGGT NINDAMLMAV
   361  QLLDSSNQEE RLPEGSVSLI ILLTDGDPTV GETNPRSIQN NVREAVSGRY SLFCLGFGFD
   421  VSYAFLEKLA LDNGGLARRI HEDSDSALQL QDFYQEVANP LLTAVTFEYP SNAVEEVTQN
   481  NFRLLFKGSE MVVAGKLQDR GPDVLTATVS GKLPTQNITF QTESSVAEQE AEFQSPKYIF
   541  HNFMERLWAY LTIQQLLEQT VSASDADQQA LRNQALNLSL AYSFVTPLTS MVVTKPDDQE
   601  QSQVAEKPME GESRNRNVHS GSTFFKYYLQ GAKIPKPEAS FSPRRGWNRQ AGAAGSRMNF
   661  RPGVLSSRQL GLPGPPDVPD HAAYHPFRRL AILPASAPPA TSNPDPAVSR VMNMKIEETT
   721  MTTQTPAPIQ APSAILPLPG QSVERLCVDP RHRQGPVNLL SDPEQGVEVT GQYEREKAGF
   781  SWIEVTFKNP LVWVHASPEH VVVTRNRRSS AYKWKETLFS VMPGLKMTMD KTGLLLLSDP
   841  DKVTIGLLFW DGRGEGLRLL LRDTDRFSSH VGGTLGQFYQ EVLWGSPAAS DDGRRTLRVQ
   901  GNDHSATRER RLDYQEGPPG VEISCWSVEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ITIH4 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: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.3
Highest tissue expression: 1,743 nTPM

Expression across tissuesHPA

Tissue

liver: 1,743 nTPM
blood vessel: 49 nTPM
pancreas: 48 nTPM
skeletal muscle: 40 nTPM
adrenal gland: 17 nTPM
bone marrow: 9.4 nTPM

Single-cell type

hepatocytes: 41 nCPM
astrocytes: 29 nCPM
myonuclei: 21 nCPM
retinal ganglion cells: 16 nCPM
brain excitatory neurons: 15 nCPM
brain inhibitory neurons: 14 nCPM

Immune cell

NK-cell: 0.4 nTPM
classical monocyte: 0.1 nTPM
memory CD4 T-cell: 0.1 nTPM
naive CD8 T-cell: 0.1 nTPM
neutrophil: 0.1 nTPM
basophil: 0 nTPM

Brain region

cerebral cortex: 3.9 nTPM
basal ganglia: 3.5 nTPM
amygdala: 3.4 nTPM
medulla oblongata: 3.3 nTPM
pons: 3.1 nTPM
white matter: 3.1 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ITIH4.

Disease | ImmuneIEDB

Conditions an epitope on ITIH4 was assayed in.

rheumatoid arthritis B and T cell
type 1 diabetes mellitus T cell

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): 0.77
gnomAD pLI: 0
gnomAD missense Z: 1.27
DepMap mean gene effect: -0.02
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ITIH4 as an antibody target. Whether an autoantibody or antibody against ITIH4 could matter depends on whether native ITIH4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ITIH4 is annotated as secreted, so native ITIH4 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label ITIH4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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