Full text data of KRT31
KRT31
(HHA1, HKA1, KRTHA1)
[Confidence: low (only semi-automatic identification from reviews)]
Keratin, type I cuticular Ha1 (Hair keratin, type I Ha1; Keratin-31; K31)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Keratin, type I cuticular Ha1 (Hair keratin, type I Ha1; Keratin-31; K31)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q15323
ID K1H1_HUMAN Reviewed; 416 AA.
AC Q15323; Q9UE12;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 14-OCT-2008, sequence version 3.
DT 22-JAN-2014, entry version 107.
DE RecName: Full=Keratin, type I cuticular Ha1;
DE AltName: Full=Hair keratin, type I Ha1;
DE AltName: Full=Keratin-31;
DE Short=K31;
GN Name=KRT31; Synonyms=HHA1, HKA1, KRTHA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hair;
RX PubMed=7578244; DOI=10.1016/0167-4781(95)00122-W;
RA Fink P., Rogers M.A., Krieg T., Winter H., Schweizer J.;
RT "A cDNA encoding the human type I hair keratin hHal.";
RL Biochim. Biophys. Acta 1264:12-14(1995).
RN [2]
RP SEQUENCE REVISION.
RA Rogers M.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=9756910; DOI=10.1074/jbc.273.41.26683;
RA Rogers M.A., Winter H., Wolf C., Heck M., Schweizer J.;
RT "Characterization of a 190-kilobase pair domain of human type I hair
RT keratin genes.";
RL J. Biol. Chem. 273:26683-26691(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=9457912; DOI=10.1046/j.1523-1747.1998.00097.x;
RA Bowden P.E., Hainey S.D., Parker G., Jones D.O., Zimonjic D.,
RA Popescu N., Hodgins M.B.;
RT "Characterization and chromosomal localization of human hair-specific
RT keratin genes and comparative expression during the hair growth
RT cycle.";
RL J. Invest. Dermatol. 110:158-164(1998).
CC -!- TISSUE SPECIFICITY: Present in scalp but not in hairless skin.
CC Abundantly expressed in the differentiating cortex of growing
CC (anagen) hair. Expression is restricted to the keratinocytes of
CC the hair cortex and is absent from inner root sheath and medulla.
CC -!- MISCELLANEOUS: There are two types of hair/microfibrillar keratin,
CC I (acidic) and II (neutral to basic).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X86570; CAA60378.1; -; mRNA.
DR EMBL; Y16787; CAA76383.1; -; Genomic_DNA.
DR EMBL; CH471152; EAW60730.1; -; Genomic_DNA.
DR EMBL; BC114468; AAI14469.1; -; mRNA.
DR PIR; S60034; S60034.
DR RefSeq; NP_002268.2; NM_002277.2.
DR UniGene; Hs.41696; -.
DR ProteinModelPortal; Q15323; -.
DR SMR; Q15323; 106-204, 274-361.
DR IntAct; Q15323; 9.
DR MINT; MINT-2860287; -.
DR STRING; 9606.ENSP00000251645; -.
DR PhosphoSite; Q15323; -.
DR DMDM; 209572740; -.
DR PaxDb; Q15323; -.
DR PRIDE; Q15323; -.
DR Ensembl; ENST00000251645; ENSP00000251645; ENSG00000094796.
DR Ensembl; ENST00000573281; ENSP00000460739; ENSG00000262993.
DR GeneID; 3881; -.
DR KEGG; hsa:3881; -.
DR UCSC; uc002hwn.3; human.
DR CTD; 3881; -.
DR GeneCards; GC17M039549; -.
DR H-InvDB; HIX0039252; -.
DR HGNC; HGNC:6448; KRT31.
DR MIM; 601077; gene.
DR neXtProt; NX_Q15323; -.
DR PharmGKB; PA30237; -.
DR eggNOG; NOG321598; -.
DR HOGENOM; HOG000230975; -.
DR HOVERGEN; HBG013015; -.
DR InParanoid; Q15323; -.
DR KO; K07604; -.
DR OMA; TKYHTEL; -.
DR OrthoDB; EOG7FV3Q8; -.
DR PhylomeDB; Q15323; -.
DR GeneWiki; KRT31; -.
DR GenomeRNAi; 3881; -.
DR NextBio; 15235; -.
DR PRO; PR:Q15323; -.
DR ArrayExpress; Q15323; -.
DR Bgee; Q15323; -.
DR CleanEx; HS_KRT31; -.
DR Genevestigator; Q15323; -.
DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR InterPro; IPR001664; IF.
DR InterPro; IPR018039; Intermediate_filament_CS.
DR InterPro; IPR002957; Keratin_I.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01248; TYPE1KERATIN.
DR PROSITE; PS00226; IF; 1.
PE 2: Evidence at transcript level;
KW Coiled coil; Complete proteome; Intermediate filament; Keratin;
KW Polymorphism; Reference proteome.
FT CHAIN 1 416 Keratin, type I cuticular Ha1.
FT /FTId=PRO_0000063684.
FT REGION 1 56 Head.
FT REGION 57 363 Rod.
FT REGION 57 91 Coil 1A.
FT REGION 92 102 Linker 1.
FT REGION 103 203 Coil 1B.
FT REGION 204 219 Linker 12.
FT REGION 220 363 Coil 2.
FT REGION 364 416 Tail.
FT SITE 305 305 Stutter.
FT VARIANT 39 39 A -> G (in dbSNP:rs6503628).
FT /FTId=VAR_046989.
FT VARIANT 82 82 A -> V (in dbSNP:rs6503627).
FT /FTId=VAR_046990.
FT VARIANT 377 377 A -> V (in dbSNP:rs34293483).
FT /FTId=VAR_046991.
FT CONFLICT 153 154 QL -> HV (in Ref. 1; CAA60378).
SQ SEQUENCE 416 AA; 47237 MW; C284DD33A4896009 CRC64;
MPYNFCLPSL SCRTSCSSRP CVPPSCHSCT LPGACNIPAN VSNCNWFCEG SFNGSEKETM
QFLNDRLASY LEKVRQLERD NAELENLIRE RSQQQEPLLC PSYQSYFKTI EELQQKILCT
KSENARLVVQ IDNAKLAADD FRTKYQTELS LRQLVESDIN GLRRILDELT LCKSDLEAQV
ESLKEELLCL KSNHEQEVNT LRCQLGDRLN VEVDAAPTVD LNRVLNETRS QYEALVETNR
REVEQWFTTQ TEELNKQVVS SSEQLQSYQA EIIELRRTVN ALEIELQAQH NLRDSLENTL
TESEARYSSQ LSQVQSLITN VESQLAEIRS DLERQNQEYQ VLLDVRARLE CEINTYRSLL
ESEDCNLPSN PCATTNACSK PIGPCLSNPC TSCVPPAPCT PCAPRPRCGP CNSFVR
//
ID K1H1_HUMAN Reviewed; 416 AA.
AC Q15323; Q9UE12;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 14-OCT-2008, sequence version 3.
DT 22-JAN-2014, entry version 107.
DE RecName: Full=Keratin, type I cuticular Ha1;
DE AltName: Full=Hair keratin, type I Ha1;
DE AltName: Full=Keratin-31;
DE Short=K31;
GN Name=KRT31; Synonyms=HHA1, HKA1, KRTHA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hair;
RX PubMed=7578244; DOI=10.1016/0167-4781(95)00122-W;
RA Fink P., Rogers M.A., Krieg T., Winter H., Schweizer J.;
RT "A cDNA encoding the human type I hair keratin hHal.";
RL Biochim. Biophys. Acta 1264:12-14(1995).
RN [2]
RP SEQUENCE REVISION.
RA Rogers M.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=9756910; DOI=10.1074/jbc.273.41.26683;
RA Rogers M.A., Winter H., Wolf C., Heck M., Schweizer J.;
RT "Characterization of a 190-kilobase pair domain of human type I hair
RT keratin genes.";
RL J. Biol. Chem. 273:26683-26691(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=9457912; DOI=10.1046/j.1523-1747.1998.00097.x;
RA Bowden P.E., Hainey S.D., Parker G., Jones D.O., Zimonjic D.,
RA Popescu N., Hodgins M.B.;
RT "Characterization and chromosomal localization of human hair-specific
RT keratin genes and comparative expression during the hair growth
RT cycle.";
RL J. Invest. Dermatol. 110:158-164(1998).
CC -!- TISSUE SPECIFICITY: Present in scalp but not in hairless skin.
CC Abundantly expressed in the differentiating cortex of growing
CC (anagen) hair. Expression is restricted to the keratinocytes of
CC the hair cortex and is absent from inner root sheath and medulla.
CC -!- MISCELLANEOUS: There are two types of hair/microfibrillar keratin,
CC I (acidic) and II (neutral to basic).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X86570; CAA60378.1; -; mRNA.
DR EMBL; Y16787; CAA76383.1; -; Genomic_DNA.
DR EMBL; CH471152; EAW60730.1; -; Genomic_DNA.
DR EMBL; BC114468; AAI14469.1; -; mRNA.
DR PIR; S60034; S60034.
DR RefSeq; NP_002268.2; NM_002277.2.
DR UniGene; Hs.41696; -.
DR ProteinModelPortal; Q15323; -.
DR SMR; Q15323; 106-204, 274-361.
DR IntAct; Q15323; 9.
DR MINT; MINT-2860287; -.
DR STRING; 9606.ENSP00000251645; -.
DR PhosphoSite; Q15323; -.
DR DMDM; 209572740; -.
DR PaxDb; Q15323; -.
DR PRIDE; Q15323; -.
DR Ensembl; ENST00000251645; ENSP00000251645; ENSG00000094796.
DR Ensembl; ENST00000573281; ENSP00000460739; ENSG00000262993.
DR GeneID; 3881; -.
DR KEGG; hsa:3881; -.
DR UCSC; uc002hwn.3; human.
DR CTD; 3881; -.
DR GeneCards; GC17M039549; -.
DR H-InvDB; HIX0039252; -.
DR HGNC; HGNC:6448; KRT31.
DR MIM; 601077; gene.
DR neXtProt; NX_Q15323; -.
DR PharmGKB; PA30237; -.
DR eggNOG; NOG321598; -.
DR HOGENOM; HOG000230975; -.
DR HOVERGEN; HBG013015; -.
DR InParanoid; Q15323; -.
DR KO; K07604; -.
DR OMA; TKYHTEL; -.
DR OrthoDB; EOG7FV3Q8; -.
DR PhylomeDB; Q15323; -.
DR GeneWiki; KRT31; -.
DR GenomeRNAi; 3881; -.
DR NextBio; 15235; -.
DR PRO; PR:Q15323; -.
DR ArrayExpress; Q15323; -.
DR Bgee; Q15323; -.
DR CleanEx; HS_KRT31; -.
DR Genevestigator; Q15323; -.
DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR InterPro; IPR001664; IF.
DR InterPro; IPR018039; Intermediate_filament_CS.
DR InterPro; IPR002957; Keratin_I.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01248; TYPE1KERATIN.
DR PROSITE; PS00226; IF; 1.
PE 2: Evidence at transcript level;
KW Coiled coil; Complete proteome; Intermediate filament; Keratin;
KW Polymorphism; Reference proteome.
FT CHAIN 1 416 Keratin, type I cuticular Ha1.
FT /FTId=PRO_0000063684.
FT REGION 1 56 Head.
FT REGION 57 363 Rod.
FT REGION 57 91 Coil 1A.
FT REGION 92 102 Linker 1.
FT REGION 103 203 Coil 1B.
FT REGION 204 219 Linker 12.
FT REGION 220 363 Coil 2.
FT REGION 364 416 Tail.
FT SITE 305 305 Stutter.
FT VARIANT 39 39 A -> G (in dbSNP:rs6503628).
FT /FTId=VAR_046989.
FT VARIANT 82 82 A -> V (in dbSNP:rs6503627).
FT /FTId=VAR_046990.
FT VARIANT 377 377 A -> V (in dbSNP:rs34293483).
FT /FTId=VAR_046991.
FT CONFLICT 153 154 QL -> HV (in Ref. 1; CAA60378).
SQ SEQUENCE 416 AA; 47237 MW; C284DD33A4896009 CRC64;
MPYNFCLPSL SCRTSCSSRP CVPPSCHSCT LPGACNIPAN VSNCNWFCEG SFNGSEKETM
QFLNDRLASY LEKVRQLERD NAELENLIRE RSQQQEPLLC PSYQSYFKTI EELQQKILCT
KSENARLVVQ IDNAKLAADD FRTKYQTELS LRQLVESDIN GLRRILDELT LCKSDLEAQV
ESLKEELLCL KSNHEQEVNT LRCQLGDRLN VEVDAAPTVD LNRVLNETRS QYEALVETNR
REVEQWFTTQ TEELNKQVVS SSEQLQSYQA EIIELRRTVN ALEIELQAQH NLRDSLENTL
TESEARYSSQ LSQVQSLITN VESQLAEIRS DLERQNQEYQ VLLDVRARLE CEINTYRSLL
ESEDCNLPSN PCATTNACSK PIGPCLSNPC TSCVPPAPCT PCAPRPRCGP CNSFVR
//
MIM
601077
*RECORD*
*FIELD* NO
601077
*FIELD* TI
*601077 KERATIN 31; KRT31
;;KERATIN, HAIR, ACIDIC, 1; KRTHA1;;
KERATIN, HARD, TYPE I, 1; HA1
read more*FIELD* TX
The keratins are a group of more than 30 proteins that belong to the
intermediate filament family. Two classes of keratins are recognized:
the epithelial keratins (e.g., 123940), or soft alpha-keratins, which
are expressed in the epidermis and the epithelia of many internal
organs, and the hair keratins, or hard alpha-keratins, which are
involved in the formation of hair and nails. Yu et al. (1993) reviewed
the human hair keratins. Electrophoretic studies have divided the hair
keratins into type I and type II subfamilies. Type I hair keratins are
acidic and have molecular masses ranging from 40 to 48 kD, and type II
hair keratins are basic to neutral and have molecular masses ranging
from 58 to 65 kD. Heid et al. (1986) identified 8 major hair keratins, 4
of each type. Additional hair keratins have subsequently been
discovered. Heid et al. (1986) and Rogers et al. (1997) commented on
hair keratin nomenclature. As with all intermediate filament subunit
proteins, the hair keratins have a common secondary structure that
consists of an N-terminal domain; 4 central alpha-helical coiled-coil
domains, denoted 1A, 1B, 2A, and 2B; and a C-terminal domain. The
non-alpha-helical domains of hair keratins have a high content of
cysteine and proline residues, the former reflecting the use of
disulfide bonding to produce a tougher, more durable structure. Sequence
comparisons show that hair keratins within a subfamily have highly
conserved alpha-helical and N-terminal domains but have C-terminal
domains that are distinct in both sequence and length. Keratins are
obligate heteropolymers, with distinct pairs of type I and type II
proteins associating to form heterodimers; these further polymerize to
produce the final 10-nm intermediate filament. Hair keratin genes are
differentially expressed in the cuticle and cortex of the hair follicle.
Langbein et al. (1999) reported the expression pattern of 9 type I hair
keratin genes in the hair follicle. Hair keratin genes are also
expressed in the tongue and thymus. The gene structures within a
subfamily are generally conserved in the number and positions of
introns, with type I genes containing 6 introns/7 exons and type II
genes containing 8 introns/9 exons. Type I hair keratin genes are
clustered on 17q12-q21, and type II genes on 12q12-q13 (Rogers et al.,
1995).
Bowden et al. (1994) isolated a human HA1 genomic clone that contains
sequences corresponding to the alpha-helical 2B domain, C-terminal
region, and 3-prime untranslated region.
By screening a human scalp cDNA library with a mouse Ha1 sequence, Fink
et al. (1995) isolated a cDNA encoding KRTHA1, or HA1. The predicted
protein has 416 amino acids, including a 49-amino acid C-terminal
domain, and a calculated molecular mass of 47.3 kD. The amino acid
sequences of the human and mouse HA1 proteins are 89% identical.
Northern blot analysis detected an approximately 1.7-kb HA1 transcript
in human scalp but not hairless skin.
By in situ hybridization, Bowden et al. (1998) showed that HA1 was
expressed in the differentiating cortex of growing (anagen) hair, with
expression beginning 2 to 3 cell layers above the apex of the dermal
papilla; expression was absent in the inner root sheath and medulla. No
HA1 expression was detected during the resting stage (telogen) of the
hair cycle.
Rogers et al. (1998) reported that the deduced KRTHA1 protein has 417
amino acids. The KRTHA1 gene contains 7 exons.
Approximately 5% of the human population express an acidic 41-kD protein
that appears in the electrophoretic pattern of their hair keratins. This
protein is inherited as an autosomal dominant trait and does not confer
a distinct hair phenotype. Winter et al. (1997) found that the 41-kD
protein is a truncated variant of HA1. They detected a G-to-A
substitution in the 5-prime splice site of intron 6 of the HA1 gene that
leads to the formation of an abnormally spliced HA1 mRNA species and the
production of an HA1 protein lacking the entire nonhelical C-terminal
domain. Winter et al. (1997) showed that the full-length and truncated
HA1 proteins form identical keratin intermediate filaments when
assembled in vitro with a type II hair keratin partner.
Rogers et al. (1998) isolated and characterized 2 overlapping human PAC
clones that cover 190 kb on 17q12-q21 and contain 9 type I hair keratin
genes, 1 transcribed hair keratin pseudogene (KRTHAP1), and 1 orphan
exon. The order of the genes is 5-prime--KRTHA6 (604540)--KRTHA5
(602764)--KRTHA2 (602760)--orphan exon--KRTHA8 (604542)--KRTHA7
(604541)--pseudogene--KRTHA1--KRTHA4 (602763)--KRTHA3B (602762)--KRTHA3A
(602761)--3-prime. The hair keratin genes range in size from 4.2 to 7.5
kb, and the genes are separated from each other by 5.5 to 18.4 kb; all
are located within about 140 kb. Each gene is transcribed from the
5-prime to 3-prime direction. Based on sequence homologies, the genes
can be grouped into 3 subclusters of tandemly arranged genes. One
subcluster, group A, consists of KRTHA1, KRTHA3A, KRTHA3B, and KRTHA4,
which share 89% overall amino acid identity. A second subcluster, group
B, contains KRTHA7 and KRTHA8, as well as the hair keratin pseudogene,
which the authors called HAA. The functional hair keratins and
hypothetical HAA hair keratin share approximately 81% overall amino acid
identity. The third subcluster, group C, consists of the structurally
less related hair keratins KRTHA2, KRTHA5, and KRTHA6, which share about
70% amino acid identity.
The KRTHAP1 pseudogene is thought to have been inactivated by a single
basepair substitution that introduced a premature TGA termination codon
into exon 4 (Winter et al., 2001). Large-scale genotyping of human,
chimpanzee, and gorilla DNAs revealed the homozygous presence of this
nonsense mutation in humans of different ethnic backgrounds, but its
absence in the functional orthologous chimpanzee and gorilla genes. The
relative numbers of synonymous and nonsynonymous substitutions in the
human pseudogene and the homologous chimpanzee gene, as inferred by
using the gorilla gene as an outgroup, suggest that the human gene was
inactivated only recently, viz., less than 240,000 years ago. This
implies that the hair keratin phenotype of hominids before that time,
and after the Pan-Homo divergence some 5.5 million years ago, could have
been identical to that of the great apes. In addition, the homozygous
presence of the exon 4 nonsense mutation in the pseudogene in some of
the earliest branching lineages among extant human populations lends
strong support to the 'single African origin' hypothesis for the
evolution of modern humans.
*FIELD* RF
1. Bowden, P. E.; Hainey, S.; Parker, G.; Hodgins, M. B.: Sequence
and expression of human hair keratin genes. J. Derm. Sci. 7 (suppl.):
S152-S163, 1994.
2. Bowden, P. E.; Hainey, S. D.; Parker, G.; Jones, D. O.; Zimonjic,
D.; Popescu, N.; Hodgins, M. B.: Characterization and chromosomal
localization of human hair-specific keratin genes and comparative
expression during the hair growth cycle. J. Invest. Derm. 110: 158-164,
1998.
3. Fink, P.; Rogers, M. A.; Korge, B.; Winter, H.; Schweizer, J.:
A cDNA encoding the human type I hair keratin hHa1. Biochim. Biophys.
Acta 1264: 12-14, 1995.
4. Heid, H. W.; Werner, E.; Franke, W. W.: The complement of native
alpha-keratin polypeptides of hair-forming cells: a subset of eight
polypeptides that differ from epithelial cytokeratins. Differentiation 32:
101-119, 1986.
5. Langbein, L.; Rogers, M. A.; Winter, H.; Silke, P.; Beckhaus, U.;
Rackwitz, H.-R.; Schweizer, J.: The catalog of human hair keratins.
I. Expression of the nine type I members in the hair follicle. J.
Biol. Chem. 274: 19874-19884, 1999.
6. Rogers, M. A.; Langbein, L.; Praetzel, S.; Moll, I.; Krieg, T.;
Winter, H.; Schweizer, J.: Sequences and differential expression
of three novel human type-II hair keratins. Differentiation 61:
187-194, 1997.
7. Rogers, M. A.; Nischt, R.; Korge, B.; Krieg, T.; Fink, T. M.; Lichter,
P.; Winter, H.; Schweizer, J.: Sequence data and chromosomal localization
of human type I and type II hair keratin genes. Exp. Cell Res. 220:
357-362, 1995.
8. Rogers, M. A.; Winter, H.; Wolf, C.; Heck, M.; Schweizer, J.:
Characterization of a 190-kilobase pair domain of human type I hair
keratin genes. J. Biol. Chem. 273: 26683-26691, 1998.
9. Winter, H.; Hofmann, I.; Langbein, L.; Rogers, M. A.; Schweizer
J.: A splice site mutation in the gene of the human type I hair keratin
hHa1 results in the expression of a tailless keratin isoform. J.
Biol. Chem. 272: 32345-32352, 1997.
10. Winter, H.; Langbein, L.; Krawczak, M.; Cooper, D. N.; Jave-Suarez,
L. F.; Rogers, M. A.; Praetzel, S.; Heidt, P. J.; Schweizer, J.:
Human type I hair keratin pseudogene phi-hHaA has functional orthologs
in the chimpanzee and gorilla: evidence for recent inactivation of
the human gene after the Pan-Homo divergence. Hum. Genet. 108: 37-42,
2001.
11. Yu, J.; Yu, D.; Checkla, D. M.; Freedberg, I. M.; Bertolino, A.
P.: Human hair keratins. J. Invest. Derm. 101 (suppl. 1): 56S-59S,
1993.
*FIELD* CN
Victor A. McKusick - updated: 1/31/2001
Patti M. Sherman - updated: 2/11/2000
Patti M. Sherman - updated: 7/14/1998
*FIELD* CD
Victor A. McKusick: 2/19/1996
*FIELD* ED
carol: 03/26/2008
mcapotos: 2/6/2001
mcapotos: 2/2/2001
terry: 1/31/2001
mgross: 2/21/2000
psherman: 2/16/2000
psherman: 2/11/2000
carol: 7/20/1998
carol: 7/14/1998
psherman: 7/8/1998
terry: 8/4/1997
terry: 7/31/1997
mark: 11/6/1996
mark: 2/19/1996
*RECORD*
*FIELD* NO
601077
*FIELD* TI
*601077 KERATIN 31; KRT31
;;KERATIN, HAIR, ACIDIC, 1; KRTHA1;;
KERATIN, HARD, TYPE I, 1; HA1
read more*FIELD* TX
The keratins are a group of more than 30 proteins that belong to the
intermediate filament family. Two classes of keratins are recognized:
the epithelial keratins (e.g., 123940), or soft alpha-keratins, which
are expressed in the epidermis and the epithelia of many internal
organs, and the hair keratins, or hard alpha-keratins, which are
involved in the formation of hair and nails. Yu et al. (1993) reviewed
the human hair keratins. Electrophoretic studies have divided the hair
keratins into type I and type II subfamilies. Type I hair keratins are
acidic and have molecular masses ranging from 40 to 48 kD, and type II
hair keratins are basic to neutral and have molecular masses ranging
from 58 to 65 kD. Heid et al. (1986) identified 8 major hair keratins, 4
of each type. Additional hair keratins have subsequently been
discovered. Heid et al. (1986) and Rogers et al. (1997) commented on
hair keratin nomenclature. As with all intermediate filament subunit
proteins, the hair keratins have a common secondary structure that
consists of an N-terminal domain; 4 central alpha-helical coiled-coil
domains, denoted 1A, 1B, 2A, and 2B; and a C-terminal domain. The
non-alpha-helical domains of hair keratins have a high content of
cysteine and proline residues, the former reflecting the use of
disulfide bonding to produce a tougher, more durable structure. Sequence
comparisons show that hair keratins within a subfamily have highly
conserved alpha-helical and N-terminal domains but have C-terminal
domains that are distinct in both sequence and length. Keratins are
obligate heteropolymers, with distinct pairs of type I and type II
proteins associating to form heterodimers; these further polymerize to
produce the final 10-nm intermediate filament. Hair keratin genes are
differentially expressed in the cuticle and cortex of the hair follicle.
Langbein et al. (1999) reported the expression pattern of 9 type I hair
keratin genes in the hair follicle. Hair keratin genes are also
expressed in the tongue and thymus. The gene structures within a
subfamily are generally conserved in the number and positions of
introns, with type I genes containing 6 introns/7 exons and type II
genes containing 8 introns/9 exons. Type I hair keratin genes are
clustered on 17q12-q21, and type II genes on 12q12-q13 (Rogers et al.,
1995).
Bowden et al. (1994) isolated a human HA1 genomic clone that contains
sequences corresponding to the alpha-helical 2B domain, C-terminal
region, and 3-prime untranslated region.
By screening a human scalp cDNA library with a mouse Ha1 sequence, Fink
et al. (1995) isolated a cDNA encoding KRTHA1, or HA1. The predicted
protein has 416 amino acids, including a 49-amino acid C-terminal
domain, and a calculated molecular mass of 47.3 kD. The amino acid
sequences of the human and mouse HA1 proteins are 89% identical.
Northern blot analysis detected an approximately 1.7-kb HA1 transcript
in human scalp but not hairless skin.
By in situ hybridization, Bowden et al. (1998) showed that HA1 was
expressed in the differentiating cortex of growing (anagen) hair, with
expression beginning 2 to 3 cell layers above the apex of the dermal
papilla; expression was absent in the inner root sheath and medulla. No
HA1 expression was detected during the resting stage (telogen) of the
hair cycle.
Rogers et al. (1998) reported that the deduced KRTHA1 protein has 417
amino acids. The KRTHA1 gene contains 7 exons.
Approximately 5% of the human population express an acidic 41-kD protein
that appears in the electrophoretic pattern of their hair keratins. This
protein is inherited as an autosomal dominant trait and does not confer
a distinct hair phenotype. Winter et al. (1997) found that the 41-kD
protein is a truncated variant of HA1. They detected a G-to-A
substitution in the 5-prime splice site of intron 6 of the HA1 gene that
leads to the formation of an abnormally spliced HA1 mRNA species and the
production of an HA1 protein lacking the entire nonhelical C-terminal
domain. Winter et al. (1997) showed that the full-length and truncated
HA1 proteins form identical keratin intermediate filaments when
assembled in vitro with a type II hair keratin partner.
Rogers et al. (1998) isolated and characterized 2 overlapping human PAC
clones that cover 190 kb on 17q12-q21 and contain 9 type I hair keratin
genes, 1 transcribed hair keratin pseudogene (KRTHAP1), and 1 orphan
exon. The order of the genes is 5-prime--KRTHA6 (604540)--KRTHA5
(602764)--KRTHA2 (602760)--orphan exon--KRTHA8 (604542)--KRTHA7
(604541)--pseudogene--KRTHA1--KRTHA4 (602763)--KRTHA3B (602762)--KRTHA3A
(602761)--3-prime. The hair keratin genes range in size from 4.2 to 7.5
kb, and the genes are separated from each other by 5.5 to 18.4 kb; all
are located within about 140 kb. Each gene is transcribed from the
5-prime to 3-prime direction. Based on sequence homologies, the genes
can be grouped into 3 subclusters of tandemly arranged genes. One
subcluster, group A, consists of KRTHA1, KRTHA3A, KRTHA3B, and KRTHA4,
which share 89% overall amino acid identity. A second subcluster, group
B, contains KRTHA7 and KRTHA8, as well as the hair keratin pseudogene,
which the authors called HAA. The functional hair keratins and
hypothetical HAA hair keratin share approximately 81% overall amino acid
identity. The third subcluster, group C, consists of the structurally
less related hair keratins KRTHA2, KRTHA5, and KRTHA6, which share about
70% amino acid identity.
The KRTHAP1 pseudogene is thought to have been inactivated by a single
basepair substitution that introduced a premature TGA termination codon
into exon 4 (Winter et al., 2001). Large-scale genotyping of human,
chimpanzee, and gorilla DNAs revealed the homozygous presence of this
nonsense mutation in humans of different ethnic backgrounds, but its
absence in the functional orthologous chimpanzee and gorilla genes. The
relative numbers of synonymous and nonsynonymous substitutions in the
human pseudogene and the homologous chimpanzee gene, as inferred by
using the gorilla gene as an outgroup, suggest that the human gene was
inactivated only recently, viz., less than 240,000 years ago. This
implies that the hair keratin phenotype of hominids before that time,
and after the Pan-Homo divergence some 5.5 million years ago, could have
been identical to that of the great apes. In addition, the homozygous
presence of the exon 4 nonsense mutation in the pseudogene in some of
the earliest branching lineages among extant human populations lends
strong support to the 'single African origin' hypothesis for the
evolution of modern humans.
*FIELD* RF
1. Bowden, P. E.; Hainey, S.; Parker, G.; Hodgins, M. B.: Sequence
and expression of human hair keratin genes. J. Derm. Sci. 7 (suppl.):
S152-S163, 1994.
2. Bowden, P. E.; Hainey, S. D.; Parker, G.; Jones, D. O.; Zimonjic,
D.; Popescu, N.; Hodgins, M. B.: Characterization and chromosomal
localization of human hair-specific keratin genes and comparative
expression during the hair growth cycle. J. Invest. Derm. 110: 158-164,
1998.
3. Fink, P.; Rogers, M. A.; Korge, B.; Winter, H.; Schweizer, J.:
A cDNA encoding the human type I hair keratin hHa1. Biochim. Biophys.
Acta 1264: 12-14, 1995.
4. Heid, H. W.; Werner, E.; Franke, W. W.: The complement of native
alpha-keratin polypeptides of hair-forming cells: a subset of eight
polypeptides that differ from epithelial cytokeratins. Differentiation 32:
101-119, 1986.
5. Langbein, L.; Rogers, M. A.; Winter, H.; Silke, P.; Beckhaus, U.;
Rackwitz, H.-R.; Schweizer, J.: The catalog of human hair keratins.
I. Expression of the nine type I members in the hair follicle. J.
Biol. Chem. 274: 19874-19884, 1999.
6. Rogers, M. A.; Langbein, L.; Praetzel, S.; Moll, I.; Krieg, T.;
Winter, H.; Schweizer, J.: Sequences and differential expression
of three novel human type-II hair keratins. Differentiation 61:
187-194, 1997.
7. Rogers, M. A.; Nischt, R.; Korge, B.; Krieg, T.; Fink, T. M.; Lichter,
P.; Winter, H.; Schweizer, J.: Sequence data and chromosomal localization
of human type I and type II hair keratin genes. Exp. Cell Res. 220:
357-362, 1995.
8. Rogers, M. A.; Winter, H.; Wolf, C.; Heck, M.; Schweizer, J.:
Characterization of a 190-kilobase pair domain of human type I hair
keratin genes. J. Biol. Chem. 273: 26683-26691, 1998.
9. Winter, H.; Hofmann, I.; Langbein, L.; Rogers, M. A.; Schweizer
J.: A splice site mutation in the gene of the human type I hair keratin
hHa1 results in the expression of a tailless keratin isoform. J.
Biol. Chem. 272: 32345-32352, 1997.
10. Winter, H.; Langbein, L.; Krawczak, M.; Cooper, D. N.; Jave-Suarez,
L. F.; Rogers, M. A.; Praetzel, S.; Heidt, P. J.; Schweizer, J.:
Human type I hair keratin pseudogene phi-hHaA has functional orthologs
in the chimpanzee and gorilla: evidence for recent inactivation of
the human gene after the Pan-Homo divergence. Hum. Genet. 108: 37-42,
2001.
11. Yu, J.; Yu, D.; Checkla, D. M.; Freedberg, I. M.; Bertolino, A.
P.: Human hair keratins. J. Invest. Derm. 101 (suppl. 1): 56S-59S,
1993.
*FIELD* CN
Victor A. McKusick - updated: 1/31/2001
Patti M. Sherman - updated: 2/11/2000
Patti M. Sherman - updated: 7/14/1998
*FIELD* CD
Victor A. McKusick: 2/19/1996
*FIELD* ED
carol: 03/26/2008
mcapotos: 2/6/2001
mcapotos: 2/2/2001
terry: 1/31/2001
mgross: 2/21/2000
psherman: 2/16/2000
psherman: 2/11/2000
carol: 7/20/1998
carol: 7/14/1998
psherman: 7/8/1998
terry: 8/4/1997
terry: 7/31/1997
mark: 11/6/1996
mark: 2/19/1996